Microwave-Assisted Solid Phase Synthesis of Different Peptide Bonds:
Recent Advancements

Munna      Mukhia; Kiran      Pradhan; Kinkar      Biswas
Abstract

Peptides are important as drugs and biologically active molecules. The synthesis of peptides has gathered considerable attention in recent years due to their various attractive properties. Conventional peptide synthesis is tedious and requires hazardous reagents and solvents. Microwave- assisted solid-phase peptide synthesis has several advantages compared with conventional batch synthesis. Herein, we have discussed various microwave-assisted solid-phase peptide bond synthesis methods developed over the last five years. Peptides are categorized into four groups - small, medium, large, and cyclic based on their length and structural characteristics to make it easier to understand. This review article also discusses the scope and limitations of microwave-assisted solid-phase peptide synthesis.
Keywords: Microwave, solid phase, peptide, protecting groups, amino acids, large peptides.
Graphical Abstract

[1]
Merrifield, R.B. Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J. Am. Chem. Soc.,  1963, 85(14), 2149-2154.
 [http://dx.doi.org/10.1021/ja00897a025]

[2]
Merrifield, B. Concept and early development of solid-phase peptide synthesis. Methods Enzymol.,  1997, 289, 3-13.
 [http://dx.doi.org/10.1016/S0076-6879(97)89040-4] [PMID:  9353714]

[3]
Mitchell, A.R. Bruce Merrifield and solid‐phase peptide synthesis: A historical assessment. Biopolymers,  2008, 90(3), 175-184.
 [http://dx.doi.org/10.1002/bip.20925] [PMID:  18213693]

[4]
Galanis, A.S.; Albericio, F.; Grøtli, M. Solid-phase peptide synthesis in water using microwave-assisted heating. Org. Lett.,  2009, 11(20), 4488-4491.
 [http://dx.doi.org/10.1021/ol901893p]

[5]
Lutz, C.; Simon, W.; Werner-Simon, S.; Pahl, A.; Müller, C. Total synthesis of α‐ and β‐amanitin. Angew. Chem. Int. Ed.,  2020, 59(28), 11390-11393.
 [http://dx.doi.org/10.1002/anie.201914935] [PMID:  32091645]

[6]
Jaradat, D.s.M.M.; Al Musaimi, O.; Albericio, F. Advances in solid-phase peptide synthesis in aqueous media (ASPPS). Green Chem.,  2022, 24(17), 6360-6372.
 [http://dx.doi.org/10.1039/D2GC02319A]

[7]
Sachdeva, S. Peptides as ‘Drugs’: The journey so far. Int. J. Pept. Res. Ther.,  2017, 23(1), 49-60.
 [http://dx.doi.org/10.1007/s10989-016-9534-8]

[8]
Bruckdorfer, T.; Marder, O.; Albericio, F. From production of peptides in milligram amounts for research to multi-tons quantities for drugs of the future. Curr. Pharm. Biotechnol.,  2004, 5(1), 29-43.
 [http://dx.doi.org/10.2174/1389201043489620] [PMID:  14965208]

[9]
Pedersen, S.W.; Armishaw, C.J.; Strømgaard, K. Synthesis of peptides using tert-butyloxycarbonyl (Boc) as the α-amino protection group. Methods Mol. Biol.,  2013, 1047, 65-80.
 [http://dx.doi.org/10.1007/978-1-62703-544-6_4] [PMID:  23943478]

[10]
Behrendt, R.; White, P.; Offer, J. Advances in Fmoc solid‐phase peptide synthesis. J. Pept. Sci.,  2016, 22(1), 4-27.
 [http://dx.doi.org/10.1002/psc.2836] [PMID:  26785684]

[11]
Rodríguez, V.; Román, J.T.; Fierro, R.; Rivera, Z.J.; García, J.E. Hydrazine hydrate: A new reagent for Fmoc group removal in solid phase peptide synthesis. Tetrahedron Lett.,  2019, 60(1), 48-51.
 [http://dx.doi.org/10.1016/j.tetlet.2018.11.054]

[12]
Merrifield, B. Solid phase synthesis. Science,  1986, 232(4748), 341-347.
 [http://dx.doi.org/10.1126/science.3961484] [PMID:  3961484]

[13]
Carpino, L.A.; Han, G.Y. 9-Fluorenylmethoxycarbonyl function, a new base-sensitive amino-protecting group. J. Am. Chem. Soc.,  1970, 92(19), 5748-5749.
 [http://dx.doi.org/10.1021/ja00722a043]

[14]
Fields, G.B.; Noble, R.L. Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids. Int. J. Pept. Protein Res.,  1990, 35(3), 161-214.
 [http://dx.doi.org/10.1111/j.1399-3011.1990.tb00939.x] [PMID:  2191922]

[15]
Hansen, A.M.; Bonke, G.; Hogendorf, W.F.J.; Björkling, F.; Nielsen, J.; Kongstad, K.T.; Zabicka, D.; Tomczak, M.; Urbas, M.; Nielsen, P.E.; Franzyk, H. Microwave-assisted solid-phase synthesis of antisense acpP peptide nucleic acid-peptide conjugates active against colistin- and tigecycline-resistant E. coli and K. pneumoniae. Eur. J. Med. Chem.,  2019, 168, 134-145.
 [http://dx.doi.org/10.1016/j.ejmech.2019.02.024] [PMID:  30807888]

[16]
El-Faham, A.; Albericio, F. Peptide coupling reagents, more than a letter soup. Chem. Rev.,  2011, 111(11), 6557-6602.
 [http://dx.doi.org/10.1021/cr100048w] [PMID:  21866984]

[17]
Wehrstedt, K.D.; Wandrey, P.A.; Heitkamp, D. Explosive properties of 1-hydroxybenzotriazoles. J. Hazard. Mater.,  2005, 126(1-3), 1-7.
 [http://dx.doi.org/10.1016/j.jhazmat.2005.05.044] [PMID:  16084016]

[18]
Subirós-Funosas, R.; Prohens, R.; Barbas, R.; El-Faham, A.; Albericio, F. Oxyma: an efficient additive for peptide synthesis to replace the benzotriazole-based HOBt and HOAt with a lower risk of explosion. Chemistry,  2009, 15(37), 9394-9403.
 [http://dx.doi.org/10.1002/chem.200900614] [PMID:  19575348]

[19]
El-Faham, A.; Funosas, R.S.Ã.; Prohens, R.; Albericio, F. COMU: A safer and more effective replacement for benzotriazole-based uronium coupling reagents. Chemistry,  2009, 15(37), 9404-9416.
 [http://dx.doi.org/10.1002/chem.200900615] [PMID:  19621394]

[20]
Subirós-Funosas, R.; Nieto-Rodriguez, L.; Jensen, K.J.; Albericio, F. COMU: scope and limitations of the latest innovation in peptide acyl transfer reagents. J. Pept. Sci.,  2013, 19(7), 408-414.
 [http://dx.doi.org/10.1002/psc.2517] [PMID:  23712932]

[21]
Albericio, F. Developments in peptide and amide synthesis. Curr. Opin. Chem. Biol.,  2004, 8(3), 211-221.
 [http://dx.doi.org/10.1016/j.cbpa.2004.03.002] [PMID:  15183318]

[22]
Pedersen, S.L.; Tofteng, A.P.; Malik, L.; Jensen, K.J. Microwave heating in solid-phase peptide synthesis. Chem. Soc. Rev.,  2012, 41(5), 1826-1844.
 [http://dx.doi.org/10.1039/C1CS15214A]

[23]
Jiang, Q-Q.; Sicking, W.; Ehlers, M.; Schmuck, C. Discovery of potent inhibitors of human β-tryptase from pre-equilibrated dynamic combinatorial libraries. Chem. Sci.,  2015, 6(3), 1792-1800.
 [http://dx.doi.org/10.1039/C4SC02943G]

[24]
Wodtke, R.; Ruiz-Gómez, G.; Kuchar, M.; Pisabarro, M.T.; Novotná, P.; Urbanová, M.; Steinbach, J.; Pietzsch, J.; Löser, R. Cyclopeptides containing the DEKS motif as conformationally restricted collagen telopeptide analogues: synthesis and conformational analysis. Org. Biomol. Chem.,  2015, 13(6), 1878-1896.
 [http://dx.doi.org/10.1039/C4OB02348J]

[25]
Witkowska, E.; Kubik, K.; Krosnicka, J.; Grabowska, K.; Niescioruk, A.; Wilenska, B.; Misicka, A. Microwave-assisted guanidinylation in solid phase peptide synthesis: comparison of various reagents. Tetrahedron Lett.,  2014, 55(45), 6198-6203.
 [http://dx.doi.org/10.1016/j.tetlet.2014.09.056]

[26]
Puckett, J.W.; Green, J.T.; Dervan, P.B. Microwave assisted synthesis of Py-Im polyamides. Org. Lett.,  2012, 14(11), 2774-2777.
 [http://dx.doi.org/10.1021/ol3010003] [PMID:  22578091]

[27]
Hojo, K.; Manabe, Y.; Uda, T.; Tsuda, Y. Water-based solid-phase peptide synthesis without hydroxy side chain protection. J. Org. Chem.,  2022, 87(17), 11362-11368.
 [http://dx.doi.org/10.1021/acs.joc.2c00828] [PMID:  35969667]

[28]
Brodrecht, M.; Herr, K.; Bothe, S.; de Oliveira, M., Jr; Gutmann, T.; Buntkowsky, G. Efficient building blocks for solid‐phase peptide synthesis of spin labeled peptides for electron paramagnetic resonance and dynamic nuclear polarization applications. ChemPhysChem,  2019, 20(11), 1475-1487.
 [http://dx.doi.org/10.1002/cphc.201900211] [PMID:  30950574]

[29]
Polese, A.; Anderson, D.J.; Millhauser, G.; Formaggio, F.; Crisma, M.; Marchiori, F.; Toniolo, C. First interchain peptide interaction detected by ESR in fully synthetic, template-assisted, two-helix bundles. J. Am. Chem. Soc.,  1999, 121(48), 11071-11078.
 [http://dx.doi.org/10.1021/ja992079h]

[30]
Jiang, J.; Yang, L.; Jin, Q.; Ma, W.; Moroder, L.; Dong, S. Site-directed spin labeling of a collagen mimetic peptide. Chemistry,  2013, 19(52), 17679-17682.
 [http://dx.doi.org/10.1002/chem.201303290] [PMID:  24273074]

[31]
Berliner, L.J.; Grunwald, J.; Hankovszky, H.O.; Hideg, K. A novel reversible thiol-specific spin label: Papain active site labeling and inhibition. Anal. Biochem.,  1982, 119(2), 450-455.
 [http://dx.doi.org/10.1016/0003-2697(82)90612-1] [PMID:  6280514]

[32]
Jaroniec, C.P. Structural studies of proteins by paramagnetic solid-state NMR spectroscopy. J. Magn. Reson.,  2015, 253, 50-59.
 [http://dx.doi.org/10.1016/j.jmr.2014.12.017] [PMID:  25797004]

[33]
Nadaud, P.S.; Helmus, J.J.; Höfer, N.; Jaroniec, C.P. Long-range structural restraints in spin-labeled proteins probed by solid-state nuclear magnetic resonance spectroscopy. J. Am. Chem. Soc.,  2007, 129(24), 7502-7503.
 [http://dx.doi.org/10.1021/ja072349t] [PMID:  17530852]

[34]
Fleissner, M.R.; Brustad, E.M.; Kálai, T.; Altenbach, C.; Cascio, D.; Peters, F.B.; Hideg, K.; Peuker, S.; Schultz, P.G.; Hubbell, W.L. Site-directed spin labeling of a genetically encoded unnatural amino acid. Proc. Natl. Acad. Sci. USA,  2009, 106(51), 21637-21642.
 [http://dx.doi.org/10.1073/pnas.0912009106] [PMID:  19995976]

[35]
Rogawski, R.; McDermott, A.E. New NMR tools for protein structure and function: Spin tags for dynamic nuclear polarization solid state NMR. Arch. Biochem. Biophys.,  2017, 628, 102-113.
 [http://dx.doi.org/10.1016/j.abb.2017.06.010] [PMID:  28623034]

[36]
Rogawski, R.; Sergeyev, I.V.; Li, Y.; Ottaviani, M.F.; Cornish, V.; McDermott, A.E. Dynamic nuclear polarization signal enhancement with high-affinity biradical tags. J. Phys. Chem. B,  2017, 121(6), 1169-1175.
 [http://dx.doi.org/10.1021/acs.jpcb.6b09021] [PMID:  28099013]

[37]
Voinov, M.A.; Good, D.B.; Ward, M.E.; Milikisiyants, S.; Marek, A.; Caporini, M.A.; Rosay, M.; Munro, R.A.; Ljumovic, M.; Brown, L.S.; Ladizhansky, V.; Smirnov, A.I. Cysteine-specific labeling of proteins with a nitroxide biradical for dynamic nuclear polarization NMR. J. Phys. Chem. B,  2015, 119(32), 10180-10190.
 [http://dx.doi.org/10.1021/acs.jpcb.5b05230] [PMID:  26230514]

[38]
Stoller, S.; Sicoli, G.; Baranova, T.Y.; Bennati, M.; Diederichsen, U. TOPP: A novel nitroxide-labeled amino acid for EPR distance measurements. Angew. Chem. Int. Ed.,  2011, 50(41), 9743-9746.
 [http://dx.doi.org/10.1002/anie.201103315] [PMID:  21898726]

[39]
Lorenzi, M.; Puppo, C.; Lebrun, R.; Lignon, S.; Roubaud, V.; Martinho, M.; Mileo, E.; Tordo, P.; Marque, S.R.A.; Gontero, B.; Guigliarelli, B.; Belle, V. Tyrosine-targeted spin labeling and EPR spectroscopy: An alternative strategy for studying structural transitions in proteins. Angew. Chem. Int. Ed.,  2011, 50(39), 9108-9111.
 [http://dx.doi.org/10.1002/anie.201102539] [PMID:  21919142]

[40]
Vitzthum, V.; Borcard, F.; Jannin, S.; Morin, M.; Miéville, P.; Caporini, M.A.; Sienkiewicz, A.; Gerber-Lemaire, S.; Bodenhausen, G. Fractional spin-labeling of polymers for enhancing NMR sensitivity by solvent-free dynamic nuclear polarization. ChemPhysChem,  2011, 12(16), 2929-2932.
 [http://dx.doi.org/10.1002/cphc.201100630] [PMID:  22028312]

[41]
Jeschke, G. Distance measurements in the nanometer range by pulse EPR. ChemPhysChem,  2002, 3(11), 927-932.
 [http://dx.doi.org/10.1002/1439-7641(20021115)3:11<927:AID-CPHC927>3.0.CO;2-Q] [PMID:  12503132]

[42]
Milov, A.D.; Ponomarev, A.B.; Tsvetkov, Y.D. Electron-electron double resonance in electron spin echo: Model biradical systems and the sensitized photolysis of decalin. Chem. Phys. Lett.,  1984, 110(1), 67-72.
 [http://dx.doi.org/10.1016/0009-2614(84)80148-7]

[43]
Martin, R.E.; Pannier, M.; Diederich, F.; Gramlich, V.; Hubrich, M.; Spiess, H.W. Determination of end-to-end distances in a series of TEMPO diradicals of up to 2.8 nm length with a new four-pulse double electron electron resonance experiment. Angew. Chem. Int. Ed.,  1998, 37(20), 2833-2837.
 [http://dx.doi.org/10.1002/(SICI)1521-3773(19981102)37:20<2833:AID-ANIE2833>3.0.CO;2-7] [PMID:  29711097]

[44]
Narr, E.; Godt, A.; Jeschke, G. Selective measurements of a nitroxide-nitroxide separation of 5 nm and a nitroxide-copper separation of 2.5 nm in a terpyridine-based copper(II) complex by pulse EPR spectroscopy. Angew. Chem. Int. Ed.,  2002, 41(20), 3907-3910.
 [http://dx.doi.org/10.1002/1521-3773(20021018)41:20<3907:AID-ANIE3907>3.0.CO;2-T] [PMID:  12386888]

[45]
Weber, A.; Schiemann, O.; Bode, B.; Prisner, T.F. PELDOR at S- and X-band frequencies and the separation of exchange coupling from dipolar coupling. J. Magn. Reson.,  2002, 157(2), 277-285.
 [http://dx.doi.org/10.1006/jmre.2002.2596] [PMID:  12323146]

[46]
Schiemann, O.; Prisner, T.F. Long-range distance determinations in biomacromolecules by EPR spectroscopy. Q. Rev. Biophys.,  2007, 40(1), 1-53.
 [http://dx.doi.org/10.1017/S003358350700460X] [PMID:  17565764]

[47]
Breinbauer, R.; Köhn, M. Azide-alkyne coupling: A powerful reaction for bioconjugate chemistry. ChemBioChem,  2003, 4(11), 1147-1149.
 [http://dx.doi.org/10.1002/cbic.200300705] [PMID:  14613105]

[48]
Kolb, H.C.; Finn, M.G.; Sharpless, K.B. Click Chemistry: Diverse chemical function from a few good reactions. Angew. Chem. Int. Ed.,  2001, 40(11), 2004-2021.
 [http://dx.doi.org/10.1002/1521-3773(20010601)40:11<2004:AID-ANIE2004>3.0.CO;2-5] [PMID:  11433435]

[49]
Kálai, T.; Fleissner, M.R. Jekő, J.; Hubbell, W.L.; Hideg, K. Synthesis of new spin labels for Cu-free click conjugation. Tetrahedron Lett.,  2011, 52(21), 2747-2749.
 [http://dx.doi.org/10.1016/j.tetlet.2011.03.077]

[50]
Kucher, S.; Korneev, S.; Tyagi, S.; Apfelbaum, R.; Grohmann, D.; Lemke, E.A.; Klare, J.P.; Steinhoff, H.J.; Klose, D. Orthogonal spin labeling using click chemistry for in vitro and in vivo applications. J. Magn. Reson.,  2017, 275, 38-45.
 [http://dx.doi.org/10.1016/j.jmr.2016.12.001] [PMID:  27992783]

[51]
Lowe, A.B. Thiol-ene “click” reactions and recent applications in polymer and materials synthesis. Polym. Chem.,  2010, 1(1), 17-36.
 [http://dx.doi.org/10.1039/B9PY00216B]

[52]
Alhassan, M.; Kumar, A.; Lopez, J.; Albericio, F.; de la Torre, B.G. Revisiting NO2 as protecting group of arginine in solid-phase peptide synthesis. Int. J. Mol. Sci.,  2020, 21(12), 4464.
 [http://dx.doi.org/10.3390/ijms21124464] [PMID:  32586051]

[53]
Futaki, S. Membrane-permeable arginine-rich peptides and the translocation mechanisms. Adv. Drug Deliv. Rev.,  2005, 57(4), 547-558.
 [http://dx.doi.org/10.1016/j.addr.2004.10.009] [PMID:  15722163]

[54]
Glasel, J.A. Basic physical properties of proteins and nucleic acids.In: Introduction to Biophysical Methods for Protein and Nucleic Acid Research; Glasel, J.A.; Deutscher, M.P.; Deutscher, M.P.; Garcia-Moreno E, B., Eds.; Academic Press,; , 1995. 

[55]
Fitch, C.A.; Platzer, G.; Okon, M.; Garcia-Moreno, E. B.; McIntosh, L.P. Arginine: Its p Ka value revisited. Protein Sci.,  2015, 24(5), 752-761.
 [http://dx.doi.org/10.1002/pro.2647] [PMID:  25808204]

[56]
Hannon, C.L.; Anslyn, E.V. Its biological role and synthetic analogs.Bioorganic Chemistry Frontiers; Dugas, H.; Schmidtchen, F.P..,Eds.; Springer Berlin Heidelberg; , 1993, pp. 193-255.
 [http://dx.doi.org/10.1007/978-3-642-78110-0_6]

[57]
Rink, H.; Sieber, P.; Raschdorf, F. Conversion of NGurethane protected arginine to ornithine in peptide solid phase synthesis. Tetrahedron Lett.,  1984, 25(6), 621-624.
 [http://dx.doi.org/10.1016/S0040-4039(00)99954-4]

[58]
Isidro-Llobet, A.; Álvarez, M.; Albericio, F. Amino acid-protecting groups. Chem. Rev.,  2009, 109(6), 2455-2504.
 [http://dx.doi.org/10.1021/cr800323s] [PMID:  19364121]

[59]
de la Torre, B.G.; Kumar, A.; Alhassan, M.; Bucher, C.; Albericio, F.; Lopez, J. Successful development of a method for the incorporation of Fmoc-Arg(Pbf)-OH in solid-phase peptide synthesis using N-butylpyrrolidinone (NBP) as solvent. Green Chem.,  2020, 22(10), 3162-3169.
 [http://dx.doi.org/10.1039/C9GC03784E]

[60]
Lopez, J.; Pletscher, S.; Aemissegger, A.; Bucher, C.; Gallou, F. N -butylpyrrolidinone as alternative solvent for solid-phase peptide synthesis. Org. Process Res. Dev.,  2018, 22(4), 494-503.
 [http://dx.doi.org/10.1021/acs.oprd.7b00389]

[61]
Schafer, D.J.; Young, G.T.; Elliott, D.F.; Wade, R. Amino-acids and peptides. Part XXXII. A simplified synthesis of bradykinin by use of the picolyl ester method. J. Chem. Soc.,  1971, 1971, 46-49.
 [http://dx.doi.org/10.1039/j39710000046]

[62]
Gros, C.; de Garilhe, M.P.; Costopanagiotis, A.; Schwyzer, R. Isolement à partir de l’hypophyse postérieure du tripeptide leucyl-arginyl-leucine et sa synthèse par une route nouvelle quant à l’incorporation de l’arginine. Helv. Chim. Acta,  1961, 44(7), 2042-2048.
 [http://dx.doi.org/10.1002/hlca.19610440730]

[63]
Kiselyov, A.S.; Smith, L.I.I.; Armstrong, R.W. Solid support synthesis of polysubstituted tetrahydroquinolines via three-component condensation catalyzed by Yb(OTf)3. Tetrahedron,  1998, 54(20), 5089-5096.
 [http://dx.doi.org/10.1016/S0040-4020(98)00248-8]

[64]
Schwarz, M.K.; Tumelty, D.; Gallop, M.A. Solid-phase synthesis of 3,5-Disubstituted 2,3-Dihydro-1,5-benzothiazepin-4(5 H)-ones. J. Org. Chem.,  1999, 64(7), 2219-2231.
 [http://dx.doi.org/10.1021/jo981567p]

[65]
Osman, S.; Jones, S.; Zewail, M.; Rabie, A.; Shalaby, A.; Howl, J. Microwave assisted peptide synthesis of some rationally designed cell penetrating peptides from C-Kit receptor. Egypt. J. Chem.,  2019, 0(0), 0.
 [http://dx.doi.org/10.21608/ejchem.2019.7119.1611]

[66]
Mäe, M.; Langel, U. Cell-penetrating peptides as vectors for peptide, protein and oligonucleotide delivery. Curr. Opin. Pharmacol.,  2006, 6(5), 509-514.
 [http://dx.doi.org/10.1016/j.coph.2006.04.004] [PMID:  16860608]

[67]
Milletti, F. Cell-penetrating peptides: Classes, origin, and current landscape. Drug Discov. Today,  2012, 17(15-16), 850-860.
 [http://dx.doi.org/10.1016/j.drudis.2012.03.002] [PMID:  22465171]

[68]
Borrelli, A.; Tornesello, A.; Tornesello, M.; Buonaguro, F. Cell penetrating peptides as molecular carriers for anti-cancer agents. Molecules,  2018, 23(2), 295.
 [http://dx.doi.org/10.3390/molecules23020295] [PMID:  29385037]

[69]
Kristensen, M.; Birch, D.; Mørck Nielsen, H. Applications and challenges for use of cell-penetrating peptides as delivery vectors for peptide and protein cargos. Int. J. Mol. Sci.,  2016, 17(2), 185.
 [http://dx.doi.org/10.3390/ijms17020185] [PMID:  26840305]

[70]
Jones, S.; Lukanowska, M.; Suhorutsenko, J.; Oxenham, S.; Barratt, C.; Publicover, S.; Copolovici, D.M.; Langel, U.; Howl, J. Intracellular translocation and differential accumulation of cell-penetrating peptides in bovine spermatozoa: evaluation of efficient delivery vectors that do not compromise human sperm motility. Hum. Reprod.,  2013, 28(7), 1874-1889.
 [http://dx.doi.org/10.1093/humrep/det064] [PMID:  23585561]

[71]
Poole, L.B. The basics of thiols and cysteines in redox biology and chemistry. Free Radic. Biol. Med.,  2015, 80, 148-157.
 [http://dx.doi.org/10.1016/j.freeradbiomed.2014.11.013] [PMID:  25433365]

[72]
Antoniou, A.I.; Pepe, D.A.; Aiello, D.; Siciliano, C.; Athanassopoulos, C.M. Chemoselective protection of glutathione in the preparation of bioconjugates: The case of trypanothione disulfide. J. Org. Chem.,  2016, 81(10), 4353-4358.
 [http://dx.doi.org/10.1021/acs.joc.6b00300] [PMID:  27137354]

[73]
Craik, D.J.; Daly, N.L.; Waine, C. The cystine knot motif in toxins and implications for drug design. Toxicon,  2001, 39(1), 43-60.
 [http://dx.doi.org/10.1016/S0041-0101(00)00160-4] [PMID:  10936622]

[74]
Hodgson, D.R.W.; Sanderson, J.M. The synthesis of peptides and proteins containing non-natural amino acids. Chem Soc Rev,  2004, 33(7), 422-430.
 [http://dx.doi.org/10.1039/b312953p]

[75]
Matsumura, M.; Signor, G.; Matthews, B.W. Substantial increase of protein stability by multiple disulphide bonds. Nature,  1989, 342(6247), 291-293.
 [http://dx.doi.org/10.1038/342291a0] [PMID:  2812028]

[76]
Muttenthaler, M.; Akondi, K.B.; Alewood, P.F. Structure-activity studies on alpha-conotoxins. Curr. Pharm. Des.,  2011, 17(38), 4226-4241.
 [http://dx.doi.org/10.2174/138161211798999384] [PMID:  22204424]

[77]
Fricker, S.P. Cysteine proteases as targets for metal-based drugs. Metallomics,  2010, 2(6), 366-377.
 [http://dx.doi.org/10.1039/b924677k] [PMID:  21072382]

[78]
Pace, N.; Weerapana, E. Zinc-binding cysteines: Diverse functions and structural motifs. Biomolecules,  2014, 4(2), 419-434.
 [http://dx.doi.org/10.3390/biom4020419] [PMID:  24970223]

[79]
Zhang, J.; Chi, Q.; Nielsen, J.U.; Friis, E.P.; Andersen, J.E.T.; Ulstrup, J. Two-dimensional cysteine and cystine cluster networks on Au(111) disclosed by voltammetry and in situ scanning tunneling microscopy. Langmuir,  2000, 16(18), 7229-7237.
 [http://dx.doi.org/10.1021/la000246h]

[80]
Banerjee, I.; Ghosh, K.C.; Oheix, E.; Jean, M.; Naubron, J.V.; Réglier, M.; Iranzo, O.; Sinha, S. Synthesis of protected 3,4- and 2,3-dimercaptophenylalanines as building blocks for Fmoc -peptide synthesis and incorporation of the 3,4-analogue in a decapeptide using solid-phase synthesis. J. Org. Chem.,  2021, 86(3), 2210-2223.
 [http://dx.doi.org/10.1021/acs.joc.0c02359] [PMID:  33491451]

[81]
Siciliano, C.; Barattucci, A.; Bonaccorsi, P.; Di Gioia, M.L.; Leggio, A.; Minuti, L.; Romio, E.; Temperini, A. Synthesis of D-erythro -sphinganine through serine-derived α-amino epoxides. J. Org. Chem.,  2014, 79(11), 5320-5326.
 [http://dx.doi.org/10.1021/jo500493c] [PMID:  24807867]

[82]
Spetzler, J.C.; Hoeg-Jensen, T. Tandem ligation at X-Cys and Gly-Gly positions via an orthogonally protected auxiliary group. Bioorg. Med. Chem.,  2007, 15(14), 4700-4704.
 [http://dx.doi.org/10.1016/j.bmc.2007.05.006] [PMID:  17507231]

[83]
Kondasinghe, T.D.; Saraha, H.Y.; Odeesho, S.B.; Stockdill, J.L. Direct palladium-mediated on-resin disulfide formation from Allocam protected peptides. Org. Biomol. Chem.,  2017, 15(14), 2914-2918.
 [http://dx.doi.org/10.1039/C7OB00536A]

[84]
Liénard, B.M.R.; Selevsek, N.; Oldham, N.J.; Schofield, C.J. Combined mass spectrometry and dynamic chemistry approach to identify metalloenzyme inhibitors. ChemMedChem,  2007, 2(2), 175-179.
 [http://dx.doi.org/10.1002/cmdc.200600250] [PMID:  17206734]

[85]
Mahendran, A.; Vuong, A.; Aebisher, D.; Gong, Y.; Bittman, R.; Arthur, G.; Kawamura, A.; Greer, A. Synthesis, characterization, mechanism of decomposition, and antiproliferative activity of a class of PEGylated benzopolysulfanes structurally similar to the natural product varacin. J. Org. Chem.,  2010, 75(16), 5549-5557.
 [http://dx.doi.org/10.1021/jo100870q] [PMID:  20704430]

[86]
Baco, E.; Hoegy, F.; Schalk, I.J.; Mislin, G.L.A. Diphenyl-benzo[1,3]dioxole-4-carboxylic acid pentafluorophenyl ester: A convenient catechol precursor in the synthesis of siderophore vectors suitable for antibiotic Trojan horse strategies. Org. Biomol. Chem.,  2014, 12(5), 749-757.
 [http://dx.doi.org/10.1039/C3OB41990H]

[87]
Kwart, H.; Evans, E.R. The vapor phase rearrangement of thioncarbonates and thioncarbamates. J. Org. Chem.,  1966, 31(2), 410-413.
 [http://dx.doi.org/10.1021/jo01340a015]

[88]
Lloyd-Jones, G.; Moseley, J.; Renny, J. Mechanism and application of the newman-kwart o→s rearrangement of O -Aryl thiocarbamates. Synthesis,  2008, 2008(5), 661-689.
 [http://dx.doi.org/10.1055/s-2008-1032179]

[89]
Miyazaki, K. The thermal rearrangement of thionocarbamates to thiolcarbamates. Tetrahedron Lett.,  1968, 9(23), 2793-2798.
 [http://dx.doi.org/10.1016/S0040-4039(00)89654-9]

[90]
Newman, M.S.; Karnes, H.A. The conversion of phenols to thiophenols via dialkylthiocarbamates. J. Org. Chem.,  1966, 31(12), 3980-3984.
 [http://dx.doi.org/10.1021/jo01350a023]

[91]
Chen, G.H.; Wang, S.; Wu, F.H. A practical synthesis of sarpogrelate hydrochloride and in vitro platelet aggregation inhibitory activities of its analogues. Chin. Chem. Lett.,  2010, 21(3), 287-289.
 [http://dx.doi.org/10.1016/j.cclet.2009.11.030]

[92]
Duttagupta, I.; Goswami, K.; Chatla, P.; Sinha, S. Improved synthesis of cyclic α -hydrazino acids of five- to nine-membered rings and optical resolution of 5,6,7-membered ring hydrazino acids. Synth. Commun.,  2014, 44(17), 2510-2519.
 [http://dx.doi.org/10.1080/00397911.2014.905601]

[93]
Duttagupta, I.; Goswami, K.; Sinha, S. Synthesis of cyclic α-hydrazino acids. Tetrahedron,  2012, 68(39), 8347-8357.
 [http://dx.doi.org/10.1016/j.tet.2012.07.014]

[94]
Duttagupta, I.; Misra, D.; Bhunya, S.; Paul, A.; Sinha, S. Cis – trans conformational analysis of δ-azaproline in peptides. J. Org. Chem.,  2015, 80(21), 10585-10604.
 [http://dx.doi.org/10.1021/acs.joc.5b01668] [PMID:  26440300]

[95]
Kelleman, A.; Mattern, R.H.; Pierschbacher, M.D.; Goodman, M. Incorporation of thioether building blocks into an αvβ3-specific RGD peptide: Synthesis and biological activity. Biopolymers,  2003, 71(6), 686-695.
 [http://dx.doi.org/10.1002/bip.10586] [PMID:  14991678]

[96]
Qu, Q.; Pan, M.; Gao, S.; Zheng, Q.Y.; Yu, Y.Y.; Su, J.C.; Li, X.; Hu, H.G. A highly efficient synthesis of polyubiquitin chains. Adv. Sci.,  2018, 5(7), 1800234.
 [http://dx.doi.org/10.1002/advs.201800234] [PMID:  30027052]

[97]
Walsh, C.T.; Garneau-Tsodikova, S.; Gatto, G.J., Jr Protein posttranslational modifications: The chemistry of proteome diversifications. Angew. Chem. Int. Ed.,  2005, 44(45), 7342-7372.
 [http://dx.doi.org/10.1002/anie.200501023] [PMID:  16267872]

[98]
Yang, R.; Liu, C.F. Chemical methods for protein ubiquitination. Top. Curr. Chem.,  2014, 362, 89-106.
 [http://dx.doi.org/10.1007/128_2014_613] [PMID:  25860252]

[99]
Hershko, A.; Ciechanover, A. The ubiquitin system. Annu. Rev. Biochem.,  1998, 67(1), 425-479.
 [http://dx.doi.org/10.1146/annurev.biochem.67.1.425] [PMID:  9759494]

[100]
Komander, D.; Rape, M. The ubiquitin code. Annu. Rev. Biochem.,  2012, 81(1), 203-229.
 [http://dx.doi.org/10.1146/annurev-biochem-060310-170328] [PMID:  22524316]

[101]
Ikeda, F.; Dikic, I. Atypical ubiquitin chains: New molecular signals. EMBO Rep.,  2008, 9(6), 536-542.
 [http://dx.doi.org/10.1038/embor.2008.93] [PMID:  18516089]

[102]
Mali, S.M.; Singh, S.K.; Eid, E.; Brik, A. Ubiquitin signaling: Chemistry comes to the rescue. J. Am. Chem. Soc.,  2017, 139(14), 4971-4986.
 [http://dx.doi.org/10.1021/jacs.7b00089] [PMID:  28328208]

[103]
Hochstrasser, M. Origin and function of ubiquitin-like proteins. Nature,  2009, 458(7237), 422-429.
 [http://dx.doi.org/10.1038/nature07958] [PMID:  19325621]

[104]
Chen, Z.J.; Sun, L.J. Nonproteolytic functions of ubiquitin in cell signaling. Mol. Cell,  2009, 33(3), 275-286.
 [http://dx.doi.org/10.1016/j.molcel.2009.01.014] [PMID:  19217402]

[105]
Li, W.; Ye, Y. Polyubiquitin chains: Functions, structures, and mechanisms. Cell. Mol. Life Sci.,  2008, 65(15), 2397-2406.
 [http://dx.doi.org/10.1007/s00018-008-8090-6] [PMID:  18438605]

[106]
Schulman, B.A.; Wade Harper, J. Ubiquitin-like protein activation by E1 enzymes: The apex for downstream signalling pathways. Nat. Rev. Mol. Cell Biol.,  2009, 10(5), 319-331.
 [http://dx.doi.org/10.1038/nrm2673] [PMID:  19352404]

[107]
Deshaies, R.J.; Joazeiro, C.A.P. RING domain E3 ubiquitin ligases. Annu. Rev. Biochem.,  2009, 78(1), 399-434.
 [http://dx.doi.org/10.1146/annurev.biochem.78.101807.093809] [PMID:  19489725]

[108]
Pickart, C.M.; Fushman, D. Polyubiquitin chains: Polymeric protein signals. Curr. Opin. Chem. Biol.,  2004, 8(6), 610-616.
 [http://dx.doi.org/10.1016/j.cbpa.2004.09.009] [PMID:  15556404]

[109]
Komander, D. The emerging complexity of protein ubiquitination. Biochem. Soc. Trans.,  2009, 37(5), 937-953.
 [http://dx.doi.org/10.1042/BST0370937] [PMID:  19754430]

[110]
Kulathu, Y.; Komander, D. Atypical ubiquitylation — the unexplored world of polyubiquitin beyond Lys48 and Lys63 linkages. Nat. Rev. Mol. Cell Biol.,  2012, 13(8), 508-523.
 [http://dx.doi.org/10.1038/nrm3394] [PMID:  22820888]

[111]
Hospenthal, M.K.; Freund, S.M.V.; Komander, D. Assembly, analysis and architecture of atypical ubiquitin chains. Nat. Struct. Mol. Biol.,  2013, 20(5), 555-565.
 [http://dx.doi.org/10.1038/nsmb.2547] [PMID:  23563141]

[112]
Jin, L.; Williamson, A.; Banerjee, S.; Philipp, I.; Rape, M. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell,  2008, 133(4), 653-665.
 [http://dx.doi.org/10.1016/j.cell.2008.04.012] [PMID:  18485873]

[113]
Todi, S.V.; Paulson, H.L. Balancing act: deubiquitinating enzymes in the nervous system. Trends Neurosci.,  2011, 34(7), 370-382.
 [http://dx.doi.org/10.1016/j.tins.2011.05.004] [PMID:  21704388]

[114]
D’Arcy, P.; Wang, X.; Linder, S. Deubiquitinase inhibition as a cancer therapeutic strategy. Pharmacol. Ther.,  2015, 147, 32-54.
 [http://dx.doi.org/10.1016/j.pharmthera.2014.11.002] [PMID:  25444757]

[115]
Meyer, H.J.; Rape, M. Enhanced protein degradation by branched ubiquitin chains. Cell,  2014, 157(4), 910-921.
 [http://dx.doi.org/10.1016/j.cell.2014.03.037] [PMID:  24813613]

[116]
Li, X.; Krafczyk, R.; Macošek, J.; Li, Y.-L.; Zou, Y.; Simon, B.; Pan, X.; Wu, Q.-Y.; Yan, F.; Li, S. Resolving the α-glycosidic linkage of arginine-rhamnosylated translation elongation factor P triggers generation of the first ArgRha specific antibody. Chem. Sci.,  2016, 7(12), 6995-7001.
 [http://dx.doi.org/10.1039/C6SC02889F]

[117]
Pan, M.; Li, S.; Li, X.; Shao, F.; Liu, L.; Hu, H.G. Synthesis of and specific antibody generation for glycopeptides with arginine N-Glc-NAcylation. Angew. Chem. Int. Ed.,  2014, 53(52), 14517-14521.
 [http://dx.doi.org/10.1002/anie.201407824] [PMID:  25353391]

[118]
Bavikar, S.N.; Spasser, L.; Haj-Yahya, M.; Karthikeyan, S.V.; Moyal, T.; Ajish Kumar, K.S.; Brik, A. Chemical synthesis of ubiquitinated peptides with varying lengths and types of ubiquitin chains to explore the activity of deubiquitinases. Angew. Chem. Int. Ed.,  2012, 51(3), 758-763.
 [http://dx.doi.org/10.1002/anie.201106430] [PMID:  22131237]

[119]
Li, X.; Li, Y.-l.; Chen, Y.; Zou, Y.; Zhuo, X.-b.; Wu, Q.-y.; Zhao, Q.-j.; Hu, H.-g. A silver-promoted solid-phase guanidylation process enables the first total synthesis of stictamide A. RSC Adv.,  2015, 5(115), 94654-94657.
 [http://dx.doi.org/10.1039/C5RA20976E]

[120]
Fang, G.M.; Li, Y.M.; Shen, F.; Huang, Y.C.; Li, J.B.; Lin, Y.; Cui, H.K.; Liu, L. Protein chemical synthesis by ligation of peptide hydrazides. Angew. Chem. Int. Ed.,  2011, 50(33), 7645-7649.
 [http://dx.doi.org/10.1002/anie.201100996] [PMID:  21648030]

[121]
Fang, G.M.; Wang, J.X.; Liu, L. Convergent chemical synthesis of proteins by ligation of peptide hydrazides. Angew. Chem. Int. Ed.,  2012, 51(41), 10347-10350.
 [http://dx.doi.org/10.1002/anie.201203843] [PMID:  22968928]

[122]
Zheng, J.S.; Tang, S.; Qi, Y.K.; Wang, Z.P.; Liu, L. Chemical synthesis of proteins using peptide hydrazides as thioester surrogates. Nat. Protoc.,  2013, 8(12), 2483-2495.
 [http://dx.doi.org/10.1038/nprot.2013.152] [PMID:  24232250]

[123]
Li, Y.M.; Li, Y.T.; Pan, M.; Kong, X.Q.; Huang, Y.C.; Hong, Z.Y.; Liu, L. Irreversible site-specific hydrazinolysis of proteins by use of sortase. Angew. Chem. Int. Ed.,  2014, 53(8), 2198-2202.
 [http://dx.doi.org/10.1002/anie.201310010] [PMID:  24470054]

[124]
Tang, S.; Si, Y.Y.; Wang, Z.P.; Mei, K.R.; Chen, X.; Cheng, J.Y.; Zheng, J.S.; Liu, L. An efficient one-pot four-segment condensation method for protein chemical synthesis. Angew. Chem. Int. Ed.,  2015, 54(19), 5713-5717.
 [http://dx.doi.org/10.1002/anie.201500051] [PMID:  25772600]

[125]
Zheng, J.S.; Yu, M.; Qi, Y.K.; Tang, S.; Shen, F.; Wang, Z.P.; Xiao, L.; Zhang, L.; Tian, C.L.; Liu, L. Expedient total synthesis of small to medium-sized membrane proteins via Fmoc chemistry. J. Am. Chem. Soc.,  2014, 136(9), 3695-3704.
 [http://dx.doi.org/10.1021/ja500222u] [PMID:  24559202]

[126]
Wang, Z.; Xu, W.; Liu, L.; Zhu, T.F. A synthetic molecular system capable of mirror-image genetic replication and transcription. Nat. Chem.,  2016, 8(7), 698-704.
 [http://dx.doi.org/10.1038/nchem.2517] [PMID:  27325097]

[127]
Pan, M.; Gao, S.; Zheng, Y.; Tan, X.; Lan, H.; Tan, X.; Sun, D.; Lu, L.; Wang, T.; Zheng, Q.; Huang, Y.; Wang, J.; Liu, L. Quasi-racemic X-ray structures of K27-linked ubiquitin chains prepared by total chemical synthesis. J. Am. Chem. Soc.,  2016, 138(23), 7429-7435.
 [http://dx.doi.org/10.1021/jacs.6b04031] [PMID:  27268299]

[128]
Wan, Q.; Danishefsky, S.J. Free-radical-based, specific desulfurization of cysteine: A powerful advance in the synthesis of polypeptides and glycopolypeptides. Angew. Chem. Int. Ed.,  2007, 46(48), 9248-9252.
 [http://dx.doi.org/10.1002/anie.200704195] [PMID:  18046687]

[129]
Jin, K.; Li, T.; Chow, H.Y.; Liu, H.; Li, X. P−B Desulfurization: An enabling method for protein chemical synthesis and site‐specific deuteration. Angew. Chem. Int. Ed.,  2017, 56(46), 14607-14611.
 [http://dx.doi.org/10.1002/anie.201709097] [PMID:  28971554]

[130]
Thomas, J.J.; Abed, M.; Heuberger, J.; Novak, R.; Zohar, Y.; Beltran Lopez, A.P.; Trausch-Azar, J.S.; Ilagan, M.X.G.; Benhamou, D.; Dittmar, G.; Kopan, R.; Birchmeier, W.; Schwartz, A.L.; Orian, A. RNF4-dependent oncogene activation by protein stabilization. Cell Rep.,  2016, 16(12), 3388-3400.
 [http://dx.doi.org/10.1016/j.celrep.2016.08.024] [PMID:  27653698]

[131]
Subirós-Funosas, R.; El-Faham, A.; Albericio, F. Aspartimide formation in peptide chemistry: Occurrence, prevention strategies and the role of N-hydroxylamines. Tetrahedron,  2011, 67(45), 8595-8606.
 [http://dx.doi.org/10.1016/j.tet.2011.08.046]

[132]
Lauer, J.L.; Fields, C.G.; Fields, G.B. Sequence dependence of aspartimide formation during 9-fluorenylmethoxycarbonyl solid-phase peptide synthesis. Lett. Pept. Sci.,  1995, 1(4), 197-205.
 [http://dx.doi.org/10.1007/BF00117955]

[133]
Neumann, K.; Farnung, J.; Baldauf, S.; Bode, J.W. Prevention of aspartimide formation during peptide synthesis using cyanosulfurylides as carboxylic acid-protecting groups. Nat. Commun.,  2020, 11(1), 982.
 [http://dx.doi.org/10.1038/s41467-020-14755-6] [PMID:  32080186]

[134]
Reusche, V.; Thomas, F. Effect of methionine sulfoxide on the synthesis and purification of aggregation‐prone peptides. ChemBioChem,  2021, 22(10), 1779-1783.
 [http://dx.doi.org/10.1002/cbic.202000865] [PMID:  33493390]

[135]
Pham, T.L.; Zilke, J.; Müller, C.C.; Thomas, F. The CSY-protecting group in the microwave-assisted synthesis of aggregation-prone peptides. RSC Chem. Biol.,  2022, 3(4), 426-430.
 [http://dx.doi.org/10.1039/D1CB00252J]

[136]
Dammers, C.; Gremer, L.; Neudecker, P.; Demuth, H.U.; Schwarten, M.; Willbold, D. Purification and characterization of recombinant n-terminally pyroglutamate-modified amyloid-β variants and structural analysis by solution NMR spectroscopy. PLoS One,  2015, 10(10), e0139710.
 [http://dx.doi.org/10.1371/journal.pone.0139710] [PMID:  26436664]

[137]
Cho, I.; Lee, H.; Lee, D.; Park, I.W.; Yoon, S.; Kim, H.Y.; Kim, Y. Solid-phase synthesis and pathological evaluation of pyroglutamate amyloid-β3-42 peptide. Sci. Rep.,  2023, 13(1), 505.
 [http://dx.doi.org/10.1038/s41598-022-26616-x] [PMID:  36627316]

[138]
Choi, J.W.; Kim, H.Y.; Jeon, M.; Kim, D.J.; Kim, Y. Efficient access to highly pure β-amyloid peptide by optimized solid-phase synthesis. Amyloid,  2012, 19(3), 133-137.
 [http://dx.doi.org/10.3109/13506129.2012.700287] [PMID:  22799493]

[139]
Marek, P.; Woys, A.M.; Sutton, K.; Zanni, M.T.; Raleigh, D.P. Efficient microwave-assisted synthesis of human islet amyloid polypeptide designed to facilitate the specific incorporation of labeled amino acids. Org. Lett.,  2010, 12(21), 4848-4851.
 [http://dx.doi.org/10.1021/ol101981b] [PMID:  20931985]

[140]
Masuda, K.; Ooyama, H.; Shikano, K.; Kondo, K.; Furumitsu, M.; Iwakoshi-Ukena, E.; Ukena, K. Microwave-assisted solid-phase peptide synthesis of neurosecretory protein GL composed of 80 amino acid residues. J. Pept. Sci.,  2015, 21(6), 454-460.
 [http://dx.doi.org/10.1002/psc.2756] [PMID:  25708449]

[141]
Driggers, E.M.; Hale, S.P.; Lee, J.; Terrett, N.K. The exploration of macrocycles for drug discovery — an underexploited structural class. Nat. Rev. Drug Discov.,  2008, 7(7), 608-624.
 [http://dx.doi.org/10.1038/nrd2590] [PMID:  18591981]

[142]
Yudin, A.K. Macrocycles: Lessons from the distant past, recent developments, and future directions. Chem. Sci.,  2015, 6(1), 30-49.
 [http://dx.doi.org/10.1039/C4SC03089C]

[143]
Fosgerau, K.; Hoffmann, T. Peptide therapeutics: Current status and future directions. Drug Discov. Today,  2015, 20(1), 122-128.
 [http://dx.doi.org/10.1016/j.drudis.2014.10.003] [PMID:  25450771]

[144]
Thapa, P.; Espiritu, M.J.; Cabalteja, C.; Bingham, J.P. The emergence of cyclic peptides: The potential of bioengineered peptide drugs. Int. J. Pept. Res. Ther.,  2014, 20(4), 545-551.
 [http://dx.doi.org/10.1007/s10989-014-9421-0]

[145]
Liras, S.; Mcclure, K.F. Permeability of cyclic peptide macrocycles and cyclotides and their potential as therapeutics. ACS Med. Chem. Lett.,  2019, 10(7), 1026-1032.
 [http://dx.doi.org/10.1021/acsmedchemlett.9b00149] [PMID:  31312403]

[146]
Tyndall, J.D.A.; Nall, T.; Fairlie, D.P. Proteases universally recognize beta strands in their active sites. Chem. Rev.,  2005, 105(3), 973-1000.
 [http://dx.doi.org/10.1021/cr040669e] [PMID:  15755082]

[147]
Hess, S.; Ovadia, O.; Shalev, D.E.; Senderovich, H.; Qadri, B.; Yehezkel, T.; Salitra, Y.; Sheynis, T.; Jelinek, R.; Gilon, C.; Hoffman, A. Effect of structural and conformation modifications, including backbone cyclization, of hydrophilic hexapeptides on their intestinal permeability and enzymatic stability. J. Med. Chem.,  2007, 50(24), 6201-6211.
 [http://dx.doi.org/10.1021/jm070836d] [PMID:  17983214]

[148]
Rezai, T.; Yu, B.; Millhauser, G.L.; Jacobson, M.P.; Lokey, R.S. Testing the conformational hypothesis of passive membrane permeability using synthetic cyclic peptide diastereomers. J. Am. Chem. Soc.,  2006, 128(8), 2510-2511.
 [http://dx.doi.org/10.1021/ja0563455] [PMID:  16492015]

[149]
Bockus, A.T.; Lexa, K.W.; Pye, C.R.; Kalgutkar, A.S.; Gardner, J.W.; Hund, K.C.R.; Hewitt, W.M.; Schwochert, J.A.; Glassey, E.; Price, D.A.; Mathiowetz, A.M.; Liras, S.; Jacobson, M.P.; Lokey, R.S. Probing the physicochemical boundaries of cell permeability and oral bioavailability in lipophilic macrocycles inspired by natural products. J. Med. Chem.,  2015, 58(11), 4581-4589.
 [http://dx.doi.org/10.1021/acs.jmedchem.5b00128] [PMID:  25950816]

[150]
Chatterjee, J.; Gilon, C.; Hoffman, A.; Kessler, H. N-methylation of peptides: A new perspective in medicinal chemistry. Acc. Chem. Res.,  2008, 41(10), 1331-1342.
 [http://dx.doi.org/10.1021/ar8000603] [PMID:  18636716]

[151]
Weide, T.; Modlinger, A.; Kessler, H. Spatial screening for the identification
of the bioactive conformation of integrinligands. In: Bioactive
Conformation I; Peters, T., Ed.; Springer Berlin Heidelberg, , 2007; pp. 1-50.
 [http://dx.doi.org/10.1007/128_052]

[152]
Hill, T.A.; Shepherd, N.E.; Diness, F.; Fairlie, D.P. Constraining cyclic peptides to mimic protein structure motifs. Angew. Chem. Int. Ed.,  2014, 53(48), 13020-13041.
 [http://dx.doi.org/10.1002/anie.201401058] [PMID:  25287434]

[153]
DeLorbe, J.E.; Clements, J.H.; Teresk, M.G.; Benfield, A.P.; Plake, H.R.; Millspaugh, L.E.; Martin, S.F. Thermodynamic and structural effects of conformational constraints in protein-ligand interactions. Entropic paradoxy associated with ligand preorganization. J. Am. Chem. Soc.,  2009, 131(46), 16758-16770.
 [http://dx.doi.org/10.1021/ja904698q] [PMID:  19886660]

[154]
Tapeinou, A.; Matsoukas, M.T.; Simal, C.; Tselios, T. Review cyclic peptides on a merry‐go‐round; towards drug design. Biopolymers,  2015, 104(5), 453-461.
 [http://dx.doi.org/10.1002/bip.22669] [PMID:  25968458]

[155]
Mallinson, J.; Collins, I. Macrocycles in new drug discovery. Future Med. Chem.,  2012, 4(11), 1409-1438.
 [http://dx.doi.org/10.4155/fmc.12.93] [PMID:  22857532]

[156]
Marsault, E.; Peterson, M.L. Macrocycles are great cycles: Applications, opportunities, and challenges of synthetic macrocycles in drug discovery. J. Med. Chem.,  2011, 54(7), 1961-2004.
 [http://dx.doi.org/10.1021/jm1012374] [PMID:  21381769]

[157]
De Leon Rodriguez, L.M.; Weidkamp, A.J.; Brimble, M.A. An update on new methods to synthesize cyclotetrapeptides. Org. Biomol. Chem.,  2015, 13(25), 6906-6921.
 [http://dx.doi.org/10.1039/C5OB00880H]

[158]
White, C.J.; Yudin, A.K. Contemporary strategies for peptide macrocyclization. Nat. Chem.,  2011, 3(7), 509-524.
 [http://dx.doi.org/10.1038/nchem.1062] [PMID:  21697871]

[159]
Davies, J.S. The cyclization of peptides and depsipeptides. J. Pept. Sci.,  2003, 9(8), 471-501.
 [http://dx.doi.org/10.1002/psc.491] [PMID:  12952390]

[160]
Lambert, J.N.; Mitchell, J.P.; Roberts, K.D. The synthesis of cyclic peptides. J. Chem. Soc., Perkin Trans. 1,  2001, 2001(5), 471-484.
 [http://dx.doi.org/10.1039/b001942i]

[161]
Jiang, S.; Li, Z.; Ding, K.; Roller, P. Recent progress of synthetic studies to peptide and peptidomimetic cyclization. Curr. Org. Chem.,  2008, 12(17), 1502-1542.
 [http://dx.doi.org/10.2174/138527208786241501]

[162]
Ng-Choi, I.; Oliveras, À.; Feliu, L.; Planas, M. Solid-phase synthesis of biaryl cyclic peptides containing a histidine-phenylalanine linkage. Int. J. Pept. Res. Ther.,  2020, 26(2), 695-707.
 [http://dx.doi.org/10.1007/s10989-019-09877-5]

[163]
Ng-Choi, I.; Oliveras, À.; Planas, M.; Feliu, L. Solid-phase synthesis of biaryl cyclic peptides containing a histidine-tyrosine linkage. Tetrahedron,  2019, 75(18), 2625-2636.
 [http://dx.doi.org/10.1016/j.tet.2019.03.014]

[164]
Schmidt, U.; Langner, J. Cyclotetrapeptides and cyclopentapeptides: Occurrence and synthesis. J. Pept. Res.,  1997, 49(1), 67-73.
 [http://dx.doi.org/10.1111/j.1399-3011.1997.tb01122.x] [PMID:  9128102]

[165]
Izumiya, N.; Kato, T.; Waki, M.; Izumiya, N.; Kato, T.; Waki, M. Synthesis of biologically active cyclic peptides. Biopolymers,  1981, 20(9), 1785-1791.
 [http://dx.doi.org/10.1002/bip.1981.360200903] [PMID:  7306667]

[166]
Schmidt, R.; Neubert, K. Cyclization studies with tetra-and pentapeptide sequences corresponding to β-casomorphins. Int. J. Pept. Protein Res.,  1991, 37(6), 502-507.
 [http://dx.doi.org/10.1111/j.1399-3011.1991.tb00767.x] [PMID:  1917307]

[167]
Malesevic, M.; Strijowski, U.; Bächle, D.; Sewald, N. An improved method for the solution cyclization of peptides under pseudo-high dilution conditions. J. Biotechnol.,  2004, 112(1-2), 73-77.
 [http://dx.doi.org/10.1016/j.jbiotec.2004.03.015] [PMID:  15288942]

[168]
Mazur, S.; Jayalekshmy, P. Chemistry of polymer-bound o-benzyne. Frequency of encounter between substituents on crosslinked polystyrenes. J. Am. Chem. Soc.,  1979, 101(3), 677-683.
 [http://dx.doi.org/10.1021/ja00497a032]

[169]
Scott, L.T.; Rebek, J.; Ovsyanko, L.; Sims, C.L. Organic chemistry on the solid phase. Site-site interactions on functionalized polystyrene. J. Am. Chem. Soc.,  1977, 99(2), 625-626.
 [http://dx.doi.org/10.1021/ja00444a060]

[170]
Kates, S.A.; Solé, N.A.; Johnson, C.R.; Hudson, D.; Barany, G.; Albericio, F. A novel, convenient, three-dimensional orthogonal strategy for solid-phase synthesis of cyclic peptides. Tetrahedron Lett.,  1993, 34(10), 1549-1552.
 [http://dx.doi.org/10.1016/0040-4039(93)85003-F]

[171]
Alsina, J.; Rabanal, F.; Giralt, E.; Albericio, F. Solid-phase synthesis of “head-to-tail” cyclic peptides via lysine side-chain anchoring. Tetrahedron Lett.,  1994, 35(51), 9633-9636.
 [http://dx.doi.org/10.1016/0040-4039(94)88531-1]

[172]
Spatola, A.F.; Darlak, K.; Romanovskis, P. An approach to cyclic peptide libraries: Reducing epimerization in medium sized rings during solid phase synthesis. Tetrahedron Lett.,  1996, 37(5), 591-594.
 [http://dx.doi.org/10.1016/0040-4039(95)02269-4]

[173]
Romanovskis, P.; Spatola, A.F. Preparation of head-to-tail cyclic peptides via side-chain attachment: Implications for library synthesis. J. Pept. Res.,  1998, 52(5), 356-374.
 [http://dx.doi.org/10.1111/j.1399-3011.1998.tb00660.x] [PMID:  9894841]

[174]
Grieco, P.; Gitu, P.M.; Hruby, V.J. Preparation of ‘side‐chain‐to‐side‐chain’ cyclic peptides by Allyl and Alloc strategy: Potential for library synthesis. J. Pept. Res.,  2001, 57(3), 250-256.
 [http://dx.doi.org/10.1111/j.1399-3011.2001.00816.x] [PMID:  11298927]

[175]
Liang, X.; Vézina-Dawod, S.; Bédard, F.; Porte, K.; Biron, E. One-pot photochemical ring-opening/cleavage approach for the synthesis and decoding of cyclic peptide libraries. Org. Lett.,  2016, 18(5), 1174-1177.
 [http://dx.doi.org/10.1021/acs.orglett.6b00296] [PMID:  26914725]

[176]
Bédard, F.; Girard, A.; Biron, É. A convenient approach to prepare topologically segregated bilayer beads for one-bead two-compound combinatorial peptide libraries. Int. J. Pept. Res. Ther.,  2013, 19(1), 13-23.
 [http://dx.doi.org/10.1007/s10989-012-9316-x]

[177]
Liang, X.; Girard, A.; Biron, E. Practical ring-opening strategy for the sequence determination of cyclic peptides from one-bead-one-compound libraries. ACS Comb. Sci.,  2013, 15(10), 535-540.
 [http://dx.doi.org/10.1021/co4000979] [PMID:  24016186]

[178]
Bourne, G.T.; Golding, S.W.; Meutermans, W.D.F.; Smythe, M.L. Synthesis of a cyclic peptide library based on the somatostatin sequence using the backbone amide linker approach. Lett. Pept. Sci.,  2000, 7(6), 311-316.
 [http://dx.doi.org/10.1023/A:1013057832044]

[179]
Alsina, J.; Jensen, K.J.; Albericio, F.; Barany, G. Solid-phase synthesis with tris(alkoxy)benzyl backbone amide linkage (BAL) [≠]. Chemistry,  1999, 5(10), 2787-2795.
 [http://dx.doi.org/10.1002/(SICI)1521-3765(19991001)5:10<2787:AID-CHEM2787>3.0.CO;2-2]

[180]
Jensen, K.J.; Alsina, J.; Songster, M.F.; Vágner, J.; Albericio, F.; Barany, G. Backbone amide linker (BAL) strategy for solid-phase synthesis of c-terminal-modified and cyclic peptides 1, 2, 3. J. Am. Chem. Soc.,  1998, 120(22), 5441-5452.
 [http://dx.doi.org/10.1021/ja974116f]

[181]
Jobin, S.; Beaumont, C.; Biron, E. Development of a solid‐phase traceless‐Ugi multicomponent reaction for backbone anchoring and cyclic peptide synthesis. Pept. Sci.,  2019, 111(1), e24044.
 [http://dx.doi.org/10.1002/pep2.24044]

[182]
Dömling, A.; Ugi, I. Multicomponent reactions with isocyanides. Angew. Chem. Int. Ed.,  2000, 39(18), 3168-3210.
 [http://dx.doi.org/10.1002/1521-3773(20000915)39:18<3168:AID-ANIE3168>3.0.CO;2-U] [PMID:  11028061]

[183]
Dömling, A. Recent developments in isocyanide based multicomponent reactions in applied chemistry. Chem. Rev.,  2006, 106(1), 17-89.
 [http://dx.doi.org/10.1021/cr0505728] [PMID:  16402771]

[184]
Lian, W.; Jiang, B.; Qian, Z.; Pei, D. Cell-permeable bicyclic peptide inhibitors against intracellular proteins. J. Am. Chem. Soc.,  2014, 136(28), 9830-9833.
 [http://dx.doi.org/10.1021/ja503710n] [PMID:  24972263]

[185]
Lian, W.; Upadhyaya, P.; Rhodes, C.A.; Liu, Y.; Pei, D. Screening bicyclic peptide libraries for protein-protein interaction inhibitors: discovery of a tumor necrosis factor-α antagonist. J. Am. Chem. Soc.,  2013, 135(32), 11990-11995.
 [http://dx.doi.org/10.1021/ja405106u] [PMID:  23865589]

[186]
Bartoloni, M.; Jin, X.; Marcaida, M.J.; Banha, J.; Dibonaventura, I.; Bongoni, S.; Bartho, K.; Gräbner, O.; Sefkow, M.; Darbre, T. Bridged bicyclic peptides as potential drug scaffolds: Synthesis, structure, protein binding and stability. Chem. Sci.,  2015, 6(10), 5473-5490.
 [http://dx.doi.org/10.1039/C5SC01699A]

[187]
Sabatino, G.; D’Ercole, A.; Pacini, L.; Zini, M.; Ribecai, A.; Paio, A.; Rovero, P.; Papini, A.M. An optimized scalable fully automated solid-phase microwave-assisted cgmp-ready process for the preparation of eptifibatide. Org. Process Res. Dev.,  2021, 25(3), 552-563.
 [http://dx.doi.org/10.1021/acs.oprd.0c00490]

[188]
Calce, E.; Vitale, R.M.; Scaloni, A.; Amodeo, P.; De Luca, S. Air oxidation method employed for the disulfide bond formation of natural and synthetic peptides. Amino Acids,  2015, 47(8), 1507-1515.
 [http://dx.doi.org/10.1007/s00726-015-1983-4] [PMID:  25900810]

[189]
Keire, D.A.; Strauss, E.; Guo, W.; Noszal, B.; Rabenstein, D.L. Kinetics and equilibria of thiol/disulfide interchange reactions of selected biological thiols and related molecules with oxidized glutathione. J. Org. Chem.,  1992, 57(1), 123-127.
 [http://dx.doi.org/10.1021/jo00027a023]

[190]
Coin, I.; Beyermann, M.; Bienert, M. Solid-phase peptide synthesis: From standard procedures to the synthesis of difficult sequences. Nat. Protoc.,  2007, 2(12), 3247-3256.
 [http://dx.doi.org/10.1038/nprot.2007.454] [PMID:  18079725]

[191]
Milton, R.C.L.; Milton, S.C.F.; Adams, P.A. Prediction of difficult sequences in solid-phase peptide synthesis. J. Am. Chem. Soc.,  1990, 112(16), 6039-6046.
 [http://dx.doi.org/10.1021/ja00172a020]

[192]
Furrer, J.; Piotto, M.; Bourdonneau, M.; Limal, D.; Guichard, G.; Elbayed, K.; Raya, J.; Briand, J.P.; Bianco, A. Evidence of secondary structure by high-resolution magic angle spinning NMR spectroscopy of a bioactive peptide bound to different solid supports. J. Am. Chem. Soc.,  2001, 123(18), 4130-4138.
 [http://dx.doi.org/10.1021/ja003566w] [PMID:  11457175]

[193]
Paradís-Bas, M.; Tulla-Puche, J.; Albericio, F. The road to the synthesis of “difficult peptides”. Chem. Soc. Rev.,  2016, 45(3), 631-654.
 [http://dx.doi.org/10.1039/C5CS00680E]

[194]
Renil, M.; Ferreras, M.; Delaisse, J.M.; Foged, N.T.; Meldal, M. PEGA supports for combinatorial peptide synthesis and solid-phase enzymatic library assays. J. Pept. Sci.,  1998, 4(3), 195-210.
 [http://dx.doi.org/10.1002/(SICI)1099-1387(199805)4:3<195:AID-PSC141>3.0.CO;2-R] [PMID:  9643628]

[195]
García-Martín, F.; Quintanar-Audelo, M.; García-Ramos, Y.; Cruz, L.J.; Gravel, C.; Furic, R.; Côté, S.; Tulla-Puche, J.; Albericio, F. ChemMatrix, a poly(ethylene glycol)-based support for the solid-phase synthesis of complex peptides. J. Comb. Chem.,  2006, 8(2), 213-220.
 [http://dx.doi.org/10.1021/cc0600019] [PMID:  16529516]

[196]
Nutt, R.F.; Brady, S.F.; Darke, P.L.; Ciccarone, T.M.; Colton, C.D.; Nutt, E.M.; Rodkey, J.A.; Bennett, C.D.; Waxman, L.H.; Sigal, I.S. Chemical synthesis and enzymatic activity of a 99-residue peptide with a sequence proposed for the human immunodeficiency virus protease. Proc. Natl. Acad. Sci.,  1988, 85(19), 7129-7133.
 [http://dx.doi.org/10.1073/pnas.85.19.7129] [PMID:  3050988]

[197]
Kresge, N.; Simoni, R.D.; Hill, R.L. The solid phase synthesis of ribonuclease a by robert bruce merrifield. ChemInform,  2006, 37(45)
 [http://dx.doi.org/10.1002/chin.200645260]

[198]
Palasek, S.A.; Cox, Z.J.; Collins, J.M. Limiting racemization and aspartimide formation in microwave-enhanced Fmoc solid phase peptide synthesis. J. Pept. Sci.,  2007, 13(3), 143-148.
 [http://dx.doi.org/10.1002/psc.804] [PMID:  17121420]

[199]
Mijalis, A.J.; Thomas, D.A., III; Simon, M.D.; Adamo, A.; Beaumont, R.; Jensen, K.F.; Pentelute, B.L. A fully automated flow-based approach for accelerated peptide synthesis. Nat. Chem. Biol.,  2017, 13(5), 464-466.
 [http://dx.doi.org/10.1038/nchembio.2318] [PMID:  28244989]
Cite As
Current Microwave Chemistry

Microwave-Assisted Solid Phase Synthesis of Different Peptide Bonds: Recent Advancements

Abstract

Graphical Abstract
