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Current Protein & Peptide Science

Author(s): Nikita Pise, Arati Prabhu*, Radhika Raheja and Illham Dhala

DOI: 10.2174/1389203723666220908150054

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Therapeutic Peptides: Unravelling Conformational Dynamics by Systematic Application of Biophysical Techniques

Page: [619 - 641] Pages: 23

  • * (Excluding Mailing and Handling)

Abstract

Peptide therapeutics represents one of the fastest-growing sectors in the pharmaceutical drugs pipeline, with an increasing number of regulatory approvals every year. Their pharmacological diversity, biocompatibility, high degree of potency and selectivity make them an attractive choice in several therapeutic areas, such as diabetes, cancer, immune, metabolic, cardiovascular and infectious diseases. However, the development of peptides as drugs presents its own set of challenges, necessitating extensive property optimization aimed at improving their drug-like properties and stability in biological environments. The discovery and development of innovative peptide therapeutic platforms entail the employment of several biophysical techniques, which monitor the structural as well as the functional integrity of peptides. Small structural changes of the bioactive peptides in response to the presence of various excipients can have a major impact on their pharmaceutical prowess, necessitating the use of analytical techniques for efficient quality control during development. Here we present some widely used methods, such as circular dichroism, fluorescence spectroscopy and multi-dimensional homo and heteronuclear nuclear magnetic resonance spectroscopy that form an integral part of therapeutic peptides development. The application of combination biophysical platforms ensures the maintenance of the appropriate folded structure, which is a prerequisite for the safety and efficacy of peptide pharmaceuticals.

Keywords: Therapeutic peptides, aggregation, conformation, dynamics, multidimensional NMR, peptide formulations

Graphical Abstract

[1]
Banting, F.G.; Best, C.H.; Collip, J.B.; Campbell, W.R.; Fletcher, A.A. Pancreatic extracts in the treatment of diabetes mellitus. Can. Med. Assoc. J., 1922, 12(3), 141-146.
[PMID: 20314060]
[2]
Elkinton, J.R.; Hunt, A.D., Jr; Godfrey, L.; Mccrory, W.W.; Rogerson, A.G.; Stokes, J. Effects of pituitary adrenocorticotropic hormone therapy. J. Am. Med. Assoc., 1949, 141(18), 1273-1279.
[http://dx.doi.org/10.1001/jama.1949.02910180001001] [PMID: 15396915]
[3]
Muttenthaler, M.; King, G.F.; Adams, D.J.; Alewood, P.F. Trends in peptide drug discovery. Nat. Rev. Drug Discov., 2021, 20(4), 309-325.
[http://dx.doi.org/10.1038/s41573-020-00135-8] [PMID: 33536635]
[4]
Al Musaimi, O.; Al Shaer, D.; Albericio, F.; de la Torre, B.; Eynde, V. 2020 FDA TIDES (Peptides and Oligonucleotides) Harvest. Pharmaceuticals, 2021, 14(2), 145.
[http://dx.doi.org/10.3390/ph14020145] [PMID: 33670364]
[5]
Torre, B.G.; Albericio, F. The pharmaceutical industry in 2020. An analysis of FDA drug approvals from the perspective of molecules. Molecules, 2021, 26(3), 627.
[http://dx.doi.org/10.3390/molecules26030627] [PMID: 33504104]
[6]
Al Shaer, D.; Al Musaimi, O.; Albericio, F.; de la Torre, B.G. 2019 FDA TIDES (Peptides and Oligonucleotides) Harvest. Pharmaceuticals, 2020, 13(3), 40.
[http://dx.doi.org/10.3390/ph13030040] [PMID: 32151051]
[7]
Lau, J.L.; Dunn, M.K. Therapeutic peptides: Historical perspectives, current development trends, and future directions. Bioorg. Med. Chem., 2018, 26(10), 2700-2707.
[http://dx.doi.org/10.1016/j.bmc.2017.06.052] [PMID: 28720325]
[8]
Henninot, A.; Collins, J.C.; Nuss, J.M. The current state of peptide drug discovery: Back to the future? J. Med. Chem., 2018, 61(4), 1382-1414.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00318] [PMID: 28737935]
[9]
Johnson, W.C. Secondary structure of proteins through circular dichroism spectroscopy. Annu. Rev. Biophys. Biophys. Chem., 1988, 17(Cd), 145-166.
[http://dx.doi.org/10.1146/annurev.bb.17.060188.001045]
[10]
Johnson, W.C. Analyzing protein circular dichroism spectra for accurate secondary structures. Proteins, 1999, 35(3), 307-312.
[http://dx.doi.org/10.1002/(SICI)1097-0134(19990515)35:3<307:AID-PROT4>3.0.CO;2-3] [PMID: 10328265]
[11]
Holzwarth, G.; Doty, P. The ultraviolet circular dichroism of polypeptides. J. Am. Chem. Soc., 1965, 87(2), 218-228.
[http://dx.doi.org/10.1021/ja01080a015] [PMID: 14228459]
[12]
Greenfield, N.J.; Fasman, G.D. Computed circular dichroism spectra for the evaluation of protein conformation. Biochemistry, 1969, 8(10), 4108-4116.
[http://dx.doi.org/10.1021/bi00838a031] [PMID: 5346390]
[13]
Noble, B.; Daniel, J.W. Applied Linear Algebra, 2nd ed; Prentice-Hall: Englewood Cliffs, London, 1977.
[14]
Provencher, S.W.; Gloeckner, J. Estimation of globular protein secondary structure from circular dichroism. Biochemistry, 1981, 20(1), 33-37.
[http://dx.doi.org/10.1021/bi00504a006] [PMID: 7470476]
[15]
Venyaminov, S.Y.; Baikalov, I.A.; Shen, Z.M.; Wu, C.S.C.; Yang, J.T. Circular dichroic analysis of denatured proteins: Inclusion of denatured proteins in the reference set. Anal. Biochem., 1993, 214(1), 17-24.
[http://dx.doi.org/10.1006/abio.1993.1450] [PMID: 8250221]
[16]
Quadrifoglio, F.; Urry, D.W. Circular dichroism and optical rotatory dispersion of gramicidins in aqueous solution. Biochem. Biophys. Res. Commun., 1967, 29(6), 785-791.
[http://dx.doi.org/10.1016/0006-291X(67)90288-4] [PMID: 6077810]
[17]
Sadhale, Y.; Shah, J.C. Stabilization of insulin against agitation-induced aggregation by the GMO cubic phase gel. Int. J. Pharm., 1999, 191(1), 51-64.
[http://dx.doi.org/10.1016/S0378-5173(99)00288-4] [PMID: 10556740]
[18]
Taschner, N.; Müller, S.A.; Alumella, V.R.; Goldie, K.N.; Drake, A.F.; Aebi, U.; Arvinte, T. Modulation of antigenicity related to changes in antibody flexibility upon lyophilization11Edited by W. Baumeister. J. Mol. Biol., 2001, 310(1), 169-179.
[http://dx.doi.org/10.1006/jmbi.2001.4736] [PMID: 11419944]
[19]
Konno, S.; Fenton, J.W., II; Villanueva, G.B. Analysis of the secondary structure of hirudin and the mechanism of its interaction with thrombin. Arch. Biochem. Biophys., 1988, 267(1), 158-166.
[http://dx.doi.org/10.1016/0003-9861(88)90019-7] [PMID: 3196024]
[20]
Kliger, Y.; Shai, Y. Inhibition of HIV-1 entry before gp41 folds into its fusion-active conformation. J. Mol. Biol., 2000, 295(2), 163-168.
[http://dx.doi.org/10.1006/jmbi.1999.3368] [PMID: 10623516]
[21]
Abragam, A.; Goldman, M.; Porneuf, M. NMR and More in Honour of Anatole Abragam, Les Editions de physique; France; , 1994, 26, . (10)
[22]
Aue, W.P.; Bartholdi, E.; Ernst, R.R. Two-dimensional spectroscopy: Application to nuclear magnetic resonance. J. Chem. Phys., 1976, 64(5), 2229.
[23]
Bax, A.; Davis, D.G. MLEV-17-Based two-dimensional homonuclear magnetization transfer spectroscopy. J. Magn. Reson., 1985, 6, 355-360.
[24]
Davis, D.G.; Bax, A. Assignment of complex proton NMR spectra via two-dimensional homonuclear Hartmann-Hahn spectroscopy. J. Am. Chem. Soc., 1985, 107(9), 2820-2821.
[http://dx.doi.org/10.1021/ja00295a052]
[25]
Macura, S.; Ernst, R.R. Elucidation of cross relaxation in liquids by two-dimensional N.M.R. spectroscopy. Mol. Phys., 1980, 41(1), 95-117.
[http://dx.doi.org/10.1080/00268978000102601]
[26]
Kumar, A.; Ernst, R.R.; Wüthrich, K. A two-dimensional nuclear overhauser enhancement (2D NOE) experiment for the elucidation of complete proton-proton cross-relaxation networks in biological macromolecules. Biochem. Biophys. Res. Commun., 1980, 95(1), 1-6.
[http://dx.doi.org/10.1016/0006-291X(80)90695-6] [PMID: 7417242]
[27]
Jeener, J.; Meier, B.H.; Bachmann, P.; Ernst, R.R. Investigation of exchange processes by two‐dimensional NMR spectroscopy. J. Chem. Phys., 1979, 71(11), 4546-4553.
[http://dx.doi.org/10.1063/1.438208]
[28]
Billeter, M.; Braun, W.K.W. Sequential resonance assignments in protein 1H nuclear magnetic resonance spectra, computation of sterically allowed proton-proton distances and statistical analysis of proton-proton distances in single cystal protein conformations. J. Mol. Biol., 1982, 155, 321-346.
[http://dx.doi.org/10.1016/0022-2836(82)90008-0] [PMID: 7077676]
[29]
Wüthrich, K.; Billeter, M.; Braun, W. Polypeptide secondary structure determination by nuclear magnetic resonance observation of short proton-proton distances. J. Mol. Biol., 1984, 180(3), 715-740.
[http://dx.doi.org/10.1016/0022-2836(84)90034-2] [PMID: 6084719]
[30]
Rance, M.; Sørensen, O.W.; Bodenhausen, G.; Wagner, G.; Ernst, R.R.; Wüthrich, K. Improved spectral resolution in COSY 1H NMR spectra of proteins via double quantum filtering. Biochem. Biophys. Res. Commun., 1983, 117(2), 479-485.
[http://dx.doi.org/10.1016/0006-291X(83)91225-1] [PMID: 6661238]
[31]
Pelczer, I. Correlation spectroscopy at a bargain: SIMPLE-COSY. J. Am. Chem. Soc., 1991, 113(8), 3211-3212.
[http://dx.doi.org/10.1021/ja00008a081]
[32]
Kay, L.; Keifer, P.; Saarinen, T. Pure absorption gradient enhanced heteronuclear single quantum correlation spectroscopy with improved sensitivity. J. Am. Chem. Soc., 1992, 114(26), 10663-10665.
[http://dx.doi.org/10.1021/ja00052a088]
[33]
Palmer, A.G., III; Cavanagh, J.; Wright, P.E.M.R. Sensitivity improvement in proton-detected two-dimensional heteronuclear correlation NMR spectroscopy. J. Magn. Reson., 1991, 93, 151-170.
[34]
Schleucher, J.; Schwendinger, M.; Sattler, M.; Schmidt, P.; Schedletzky, O.; Glaser, S.J.; Sørensen, O.W.; Griesinger, C. A general enhancement scheme in heteronuclear multidimensional NMR employing pulsed field gradients. J. Biomol. NMR, 1994, 4(2), 301-306.
[http://dx.doi.org/10.1007/BF00175254] [PMID: 8019138]
[35]
Clore, G.M.; Gronenborn, A.M.; Brünger, A.T.; Karplus, M. Solution conformation of a heptadecapeptide comprising the DNA binding helix F of the cyclic AMP receptor protein of Escherichia coli. J. Mol. Biol., 1985, 186(2), 435-455.
[http://dx.doi.org/10.1016/0022-2836(85)90116-0] [PMID: 3910844]
[36]
Wishart, D.S.; Sykes, B.D.; Richards, F.M. The chemical shift index: A fast and simple method for the assignment of protein secondary structure through NMR spectroscopy. Biochemistry, 1992, 31(6), 1647-1651.
[http://dx.doi.org/10.1021/bi00121a010] [PMID: 1737021]
[37]
Bach, A.C., II; Eyermann, C.J.; Gross, J.D.; Bower, M.J.; Harlow, R.L.; Weber, P.C.; DeGrado, W.F. Structural studies of a family of high affinity ligands for GPIIb/IIIa. J. Am. Chem. Soc., 1994, 116(8), 3207-3219.
[http://dx.doi.org/10.1021/ja00087a006]
[38]
Karplus, M. Contact electron‐spin coupling of nuclear magnetic moments. J. Chem. Phys., 1959, 30(1), 11-15.
[http://dx.doi.org/10.1063/1.1729860]
[39]
Vuister, G.W.; Bax, A. Quantitative J correlation: A new approach for measuring homonuclear three-bond J(HNH.α.) coupling constants in 15N-enriched proteins. J. Am. Chem. Soc., 1993, 115(17), 7772-7777.
[http://dx.doi.org/10.1021/ja00070a024]
[40]
Boelens, R.; Koning, T.M.G.; Marel, G.A.; Van, B.H.K.R. Iterative procedure for structure determination from proton-proton NOEs using a relaxation matrix approach, application to a DNA octamer. J. Magn. Reson., 1989, 82, 290.
[41]
Boelens, R.; Koning, T.M.G.; Kaptein, R. Determination of biomolecular structures from proton-proton NOE’s using a relaxation matrix approach. J. Mol. Struct., 1988, 173, 299-311.
[http://dx.doi.org/10.1016/0022-2860(88)80062-0]
[42]
Koning, T. IRMA: Iterative realxation matrix approach for NMR structure determination applications to DNA fragments. 1990, 22(2), 169.
[43]
Lipari, G.; Model-Free, S.A. Appraoach to the interpretation of nuclear magnetic relaxation in macromolecules. J. Am. Chem. Soc., 1982, 1104, 45446.
[44]
Bruch, M.D.; Cajal, Y.; Koh, J.T.; Jain, M.K. Higher-order structure of polymyxin B: The functional significance of topological flexibility. J. Am. Chem. Soc., 1999, 121(51), 11993-12004.
[http://dx.doi.org/10.1021/ja992376m]
[45]
Choules, M.P.; Bisson, J.; Gao, W.; Lankin, D.C.; McAlpine, J.B.; Niemitz, M.; Jaki, B.U.; Franzblau, S.G.; Pauli, G.F. Quality control of therapeutic peptides by 1 H NMR HiFSA sequencing. J. Org. Chem., 2019, 84(6), 3055-3073.
[http://dx.doi.org/10.1021/acs.joc.8b02704] [PMID: 30793905]
[46]
Barden, J.A.; Kemp, B.E. NMR solution structure of human parathyroid hormone(1-34). Biochemistry, 1993, 32(28), 7126-7132.
[http://dx.doi.org/10.1021/bi00079a008] [PMID: 8343504]
[47]
Takács, I.; Jókai, E.; Kováts, D.E.; Aradi, I. The first biosimilar approved for the treatment of osteoporosis: Results of a comparative pharmacokinetic/pharmacodynamic study. Osteoporos. Int., 2019, 30(3), 675-683.
[http://dx.doi.org/10.1007/s00198-018-4741-0] [PMID: 30357438]
[48]
Kovács, P.; Schäfer, T.; Háda, V.; Hevér, H.; Klingelhöfer, S.; Nebel, M.; Stadie, T.; Kiss, R.; Urbányi, Z. Comparative physicochemical and biological characterisation of the similar biological medicinal product teriparatide and its reference medicinal product. BioDrugs, 2020, 34(1), 65-75.
[http://dx.doi.org/10.1007/s40259-019-00386-x] [PMID: 31595483]
[49]
Dole, M.; Mack, L.L.; Hines, R.L.; Mobley, R.C.; Ferguson, L.D.; Alice, M.B.; Alice, M.B. Molecular beams of macroions. J. Chem. Phys., 1968, 49(5), 2240-2249.
[http://dx.doi.org/10.1063/1.1670391]
[50]
Karas, M.; Bachmann, D.; Bahr, U.; Hillenkamp, F. Matrix-assisted ultraviolet laser desorption of non-volatile compounds. Int. J. Mass Spectrom. Ion Process., 1987, 78, 53-68.
[http://dx.doi.org/10.1016/0168-1176(87)87041-6]
[51]
Cohen, S.L.; Chait, B.T. Influence of matrix solution conditions on the MALDI-MS analysis of peptides and proteins. Anal. Chem., 1996, 68(1), 31-37.
[http://dx.doi.org/10.1021/ac9507956] [PMID: 8779435]
[52]
Beavis, R.C.; Chait, B.T. Matrix-assisted laser desorption ionization mass-spectrometry of proteins. Methods Enzymol., 1996, 270, 519-551.
[http://dx.doi.org/10.1016/S0076-6879(96)70024-1] [PMID: 8803983]
[53]
Clore, G.M.; Gronenborn, A.M. Applications of three- and four-dimensional heteronuclear NMR spectroscopy to protein structure determination. Prog. Nucl. Magn. Reson. Spectrosc., 1991, 23(1), 43-92.
[http://dx.doi.org/10.1016/0079-6565(91)80002-J]
[54]
Griesinger, C.; Sorensen, O.W.; Ernst, R.R. Novel three-dimensional NMR techniques for studies of peptides and biological macromolecules. J. Am. Chem. Soc., 1987, 109(23), 7227-7228.
[http://dx.doi.org/10.1021/ja00257a074]
[55]
Oschkinat, H.; Griesinger, C.; Kraulis, P.J.; Sørensen, O.W.; Ernst, R.R.; Gronenborn, A.M.; Clore, G.M. Three-dimensional NMR spectroscopy of a protein in solution. Nat., 1988, 332(6162), 374-376.
[http://dx.doi.org/10.1038/332374a0]
[56]
Wüthrich, K. Protein structure determination in solution by nuclear magnetic resonance spectroscopy. Science, 1989, 243(4887), 45-50.
[http://dx.doi.org/10.1126/science.2911719] [PMID: 2911719]
[57]
Bax, A.; Grzesiek, S. Methodological advances in protein NMR. Acc. Chem. Res., 1993, 26(4), 131-138.
[http://dx.doi.org/10.1021/ar00028a001]
[58]
Powers, R.; Gronenborn, A.M.; Clore, G. Marius; Bax, A.D. Three-dimensional triple-resonance NMR of 13C/15N-enriched proteins using constant-time evolution. J. Magn. Reson., 1991, 94, 209-213.
[59]
Ikura, M.; Kay, L.E.; Bax, A. A novel approach for sequential assignment of 1H, 13C, and 15N spectra of proteins: Heteronuclear triple-resonance three-dimensional NMR spectroscopy. Application to calmodulin. Biochemistry, 1990, 29(19), 4659-4667.
[http://dx.doi.org/10.1021/bi00471a022] [PMID: 2372549]
[60]
Kay, L.E.; Gardner, K.H. Solution NMR spectroscopy beyond 25 kDa. Curr. Opin. Struct. Biol., 1997, 7(5), 722-731.
[http://dx.doi.org/10.1016/S0959-440X(97)80084-X] [PMID: 9345633]
[61]
Sattler, M.; Schleucher, J.; Griesinger, C. Heteronuclear multidimensional NMR experiments for the structure determination of proteins in solution employing pulsed field gradients. Prog. Nucl. Magn. Reson. Spectrosc., 1999, 34(2), 93-158.
[http://dx.doi.org/10.1016/S0079-6565(98)00025-9]
[62]
Kay, L.E.; Ikura, M.; Tschudin, R.; Bax, A. Three-dimensional triple-resonance NMR spectroscopy of isotopically enriched proteins. J. Magn. Reson., 1990, 89(3), 496-514.
[http://dx.doi.org/10.1016/0022-2364(90)90333-5] [PMID: 22152361]
[63]
Grzesiek, S.; Bax, A. Improved 3D triple-resonance NMR techniques applied to a 31 kDa protein. J. Magn. Reson., 1992, 96(2), 432-440.
[http://dx.doi.org/10.1016/0022-2364(92)90099-S]
[64]
Bax, A.; Ikura, M. An efficient 3D NMR technique for correlating the proton and15N backbone amide resonances with the α-carbon of the preceding residue in uniformly15N/13C enriched proteins. J. Biomol. NMR, 1991, 1(1), 99-104.
[http://dx.doi.org/10.1007/BF01874573] [PMID: 1668719]
[65]
Logan, T.M.; Zhou, M.M.; Nettesheim, D.G.; Meadows, R.P.; Van Etten, R.L.; Fesik, S.W. Solution structure of a low molecular weight protein tyrosine phosphatase. Biochemistry, 1994, 33(37), 11087-11096.
[http://dx.doi.org/10.1021/bi00203a005] [PMID: 7727361]
[66]
Hennig, M.; Bermel, W.; Spencer, A.; Dobson, C.M.; Smith, L.J.; Schwalbe, H. Side-chain conformations in an unfolded protein: Χ 1 distributions in denatured hen lysozyme determined by heteronuclear 13C, 15N NMR spectroscopy 1 1Edited by A. R. Fersht. J. Mol. Biol., 1999, 288(4), 705-723.
[http://dx.doi.org/10.1006/jmbi.1999.2722] [PMID: 10329174]
[67]
Zhang, O.; Forman-Kay, J.D. NMR studies of unfolded states of an SH3 domain in aqueous solution and denaturing conditions. Biochemistry, 1997, 36(13), 3959-3970.
[http://dx.doi.org/10.1021/bi9627626] [PMID: 9092826]
[68]
Panchal, S.C.; Bhavesh, N.S.; Hosur, R.V. Improved 3D triple resonance experiments, HNN and HN(C)N, for HN and 15N sequential correlations in (13C, 15N) labeled proteins: Application to unfolded proteins. J. Biomol. NMR, 2001, 20(2), 135-147.
[http://dx.doi.org/10.1023/A:1011239023422] [PMID: 11495245]
[69]
Bax, A.; Vuister, G.W.; Grzesiek, S.; Delaglio, F.; Wang, A.C.; Tschudin, R.; Zhu, G. Measurement of homo- and heteronuclear J couplings from quantitative J correlation. Methods Enzymol., 1994, 239(C), 79-105.
[http://dx.doi.org/10.1016/S0076-6879(94)39004-5] [PMID: 7830604]
[70]
Zhang, F.; Adnani, N.; Vazquez-Rivera, E.; Braun, D.R.; Tonelli, M.; Andes, D.R.; Bugni, T.S. Application of 3D NMR for structure determination of peptide natural products. J. Org. Chem., 2015, 80(17), 8713-8719.
[http://dx.doi.org/10.1021/acs.joc.5b01486] [PMID: 26273993]
[71]
Wang, G. Structures of human host defense cathelicidin LL-37 and its smallest antimicrobial peptide KR-12 in lipid micelles. J. Biol. Chem., 2008, 283(47), 32637-32643.
[http://dx.doi.org/10.1074/jbc.M805533200] [PMID: 18818205]
[72]
Anfinsen, C.B.; Haber, E.; Sela, M.; White, F.H., Jr The kinetics of formation of native ribonuclease during oxidation of the reduced polypeptide chain. Proc. Natl. Acad. Sci., 1961, 47(9), 1309-1314.
[http://dx.doi.org/10.1073/pnas.47.9.1309] [PMID: 13683522]
[73]
Anfinsen, C.B. Principles that govern the folding of protein chains. Science, 1973, 181(4096), 223-230.
[http://dx.doi.org/10.1126/science.181.4096.223] [PMID: 4124164]
[74]
Šali, A.; Shakhnovich, E.; Karplus, M. Kinetics of protein folding. A lattice model study of the requirements for folding to the native state. J. Mol. Biol., 1994, 235(5), 1614-1636.
[http://dx.doi.org/10.1006/jmbi.1994.1110] [PMID: 8107095]
[75]
Plotkin, S.S.; Onuchic, J.N. Understanding protein folding with energy landscape theory Part I: Basic concepts. Q. Rev. Biophys., 2002, 35(2), 111-167.
[http://dx.doi.org/10.1017/S0033583502003761] [PMID: 12197302]
[76]
Dill, K.A.; Chan, H.S. From Levinthal to pathways to funnels. Nat. Struct. Mol. Biol., 1997, 4(1), 10-19.
[http://dx.doi.org/10.1038/nsb0197-10] [PMID: 8989315]
[77]
Wolynes, P.G.; Onuchic, J.N.; Thirumalai, D. Navigating the folding routes. Science, 1995, 267(5204), 1619-1620.
[http://dx.doi.org/10.1126/science.7886447] [PMID: 7886447]
[78]
Bryngelson, J.D.; Onuchic, J.N.; Socci, N.D.; Wolynes, P.G. Funnels, pathways, and the energy landscape of protein folding: A synthesis. Proteins, 1995, 21(3), 167-195.
[http://dx.doi.org/10.1002/prot.340210302] [PMID: 7784423]
[79]
Leopold, P.E.; Montal, M.; Onuchic, J.N. Protein folding funnels: A kinetic approach to the sequence-structure relationship. Proc. Natl. Acad. Sci., 1992, 89(18), 8721-8725.
[http://dx.doi.org/10.1073/pnas.89.18.8721] [PMID: 1528885]
[80]
Bryngelson, J.D.; Wolynes, P.G. Spin glasses and the statistical mechanics of protein folding. Proc. Natl. Acad. Sci., 1987, 84(21), 7524-7528.
[http://dx.doi.org/10.1073/pnas.84.21.7524] [PMID: 3478708]
[81]
Avadisian, M.; Gunning, P.T. Extolling the benefits of molecular therapeutic lipidation. Mol. Biosyst., 2013, 9(9), 2179-2188.
[http://dx.doi.org/10.1039/c3mb70147f] [PMID: 23771042]
[82]
Ward, B.P.; Ottaway, N.L.; Perez-Tilve, D.; Ma, D.; Gelfanov, V.M.; Tschöp, M.H.; DiMarchi, R.D. Peptide lipidation stabilizes structure to enhance biological function. Mol. Metab., 2013, 2(4), 468-479.
[http://dx.doi.org/10.1016/j.molmet.2013.08.008] [PMID: 24327962]
[83]
Li, Y.; Wang, Y.; Wei, Q.; Zheng, X.; Tang, L.; Kong, D.; Gong, M. Variant fatty acid-like molecules Conjugation, novel approaches for extending the stability of therapeutic peptides. Sci. Rep., 2016, 5(1), 18039.
[http://dx.doi.org/10.1038/srep18039] [PMID: 26658631]
[84]
Aicart-Ramos, C.; Valero, R.A.; Rodriguez-Crespo, I. Protein palmitoylation and subcellular trafficking. Biochim. Biophys. Acta Biomembr., 2011, 1808(12), 2981-2994.
[http://dx.doi.org/10.1016/j.bbamem.2011.07.009] [PMID: 21819967]
[85]
Li, Y.; Zheng, X.; Tang, L.; Xu, W.; Gong, M. GLP-1 analogs containing disulfide bond exhibited prolonged half-life in vivo than GLP-1. Peptides, 2011, 32(6), 1303-1312.
[http://dx.doi.org/10.1016/j.peptides.2011.04.001] [PMID: 21515323]
[86]
Vinther, T.N.; Kjeldsen, T.B.; Jensen, K.J.; Hubálek, F. The road to the first, fully active and more stable human insulin variant with an additional disulfide bond. J. Pept. Sci., 2015, 21(11), 797-806.
[http://dx.doi.org/10.1002/psc.2822] [PMID: 26382042]
[87]
Nick Pace, C.; Scholtz, J.M.; Grimsley, G.R. Forces stabilizing proteins. FEBS Lett., 2014, 588(14), 2177-2184.
[http://dx.doi.org/10.1016/j.febslet.2014.05.006] [PMID: 24846139]
[88]
Hagihara, Y.; Saerens, D. Engineering disulfide bonds within an antibody. Biochim. Biophys. Acta. Proteins Proteomics, 2014, 1844(11), 2016-2023.
[http://dx.doi.org/10.1016/j.bbapap.2014.07.005] [PMID: 25038323]
[89]
Furman, J.L.; Chiu, M.; Hunter, M.J. Early engineering approaches to improve peptide developability and manufacturability. AAPS J., 2015, 17(1), 111-120.
[http://dx.doi.org/10.1208/s12248-014-9681-9] [PMID: 25338742]
[90]
Qvit, N.; Rubin, S.J.S.; Urban, T.J.; Mochly-Rosen, D.; Gross, E.R. Peptidomimetic therapeutics: Scientific approaches and opportunities. Drug Discov. Today, 2017, 22(2), 454-462.
[http://dx.doi.org/10.1016/j.drudis.2016.11.003] [PMID: 27856346]
[91]
Greenfield, N.J. Using circular dichroism spectra to estimate protein secondary structure. Nat. Protoc., 2006, 1(6), 2876-2890.
[http://dx.doi.org/10.1038/nprot.2006.202] [PMID: 17406547]
[92]
Woody, R.W. Circular dichroism spectrum of peptides in the poly(Pro)II conformation. J. Am. Chem. Soc., 2009, 131(23), 8234-8245.
[http://dx.doi.org/10.1021/ja901218m] [PMID: 19462996]
[93]
Tifany, M.L.; Krimm, S. Effect of temperature on the circular dichroism spectra of polypeptides in the extended state. Biopolymers, 1972, 11(11), 2309-2316.
[http://dx.doi.org/10.1002/bip.1972.360111109] [PMID: 4634868]
[94]
Chen, Y.; Barkley, M.D. Toward understanding tryptophan fluorescence in proteins. Biochemistry, 1998, 37(28), 9976-9982.
[http://dx.doi.org/10.1021/bi980274n] [PMID: 9665702]
[95]
Colucci, W.J.; Tilstra, L.; Sattler, M.C.; Fronczek, F.R.; Barkley, M.D. Conformational studies of a constrained tryptophan derivative: Implications for the fluorescence quenching mechanism. J. Am. Chem. Soc., 1990, 112(25), 9182-9190.
[http://dx.doi.org/10.1021/ja00181a022]
[96]
Lainé, A.L.; Houvenagel, S.; Broo, A.; Jones, I.; Goodman, J.; Corkill, D.; Rose, J.; Coward, S.; Sandinge, A.S.; Petrone, M.; Jermutus, L.; Santos, A.L.G.D. Developing an injectable co-formulation of two antidiabetic drugs: Excipient impact on peptide aggregation and pharmacokinetic properties. Int. J. Pharm., 2020, 576, 119019.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119019] [PMID: 31911116]
[97]
Smyth, M.S.; Martin, J.H.J. X Ray crystallography. Mol. Pathol., 2000, 53(1), 8-14.
[http://dx.doi.org/10.1136/mp.53.1.8] [PMID: 10884915]
[98]
Schmidt, M.; Pahl, R.; Srajer, V.; Anderson, S.; Brister, K.; Ruan, S.; Rajagopal, S.; Ren, Z.; Moffat, K. Application of singular value decomposition to time-resolved X-ray data; simulations and experiments. Acta Crystallogr. A, 2002, 58(S1), c374.
[http://dx.doi.org/10.1107/S0108767302099956]
[99]
McPherson, A.; Malkin, A.J.; Kuznetsov, Y.G.; Plomp, M. Atomic force microscopy applications in macromolecular crystallography. Acta Crystallogr. D Biol. Crystallogr., 2001, 57(8), 1053-1060.
[http://dx.doi.org/10.1107/S0907444901008824] [PMID: 11468388]
[100]
Yip, C.M. Atomic force microscopy of macromolecular interactions. Curr. Opin. Struct. Biol., 2001, 11(5), 567-572.
[http://dx.doi.org/10.1016/S0959-440X(00)00247-5] [PMID: 11785757]
[101]
Baumeister, W.; Steven, A.C. Macromolecular electron microscopy in the era of structural genomics. Trends Biochem. Sci., 2000, 25(12), 624-631.
[http://dx.doi.org/10.1016/S0968-0004(00)01720-5] [PMID: 11116190]
[102]
Levy, R.M.; Sheridan, R.P.; Keepers, J.W.; Dubey, G.S.; Swaminathan, S.; Karplus, M. Molecular dynamics of myoglobin at 298 degrees K. Results from a 300-ps computer simulation. Biophys. J., 1985, 48(3), 509-518.
[http://dx.doi.org/10.1016/S0006-3495(85)83806-6] [PMID: 3840041]
[103]
Kay, L.E.; Torchia, D.A.; Bax, A. Backbone dynamics of proteins as studied by nitrogen-15 inverse detected heteronuclear NMR spectroscopy: Application to staphylococcal nuclease. Biochemistry, 1989, 28(23), 8972-8979.
[http://dx.doi.org/10.1021/bi00449a003] [PMID: 2690953]
[104]
McCain, D.C.; Ulrich, E.L.; Markley, J.L. NMR relaxation study of internal motions in Staphylococcal nuclease. J. Magn. Reson., 1988, 80(2), 296-305.
[http://dx.doi.org/10.1016/0022-2364(88)90298-3]
[105]
Olejniczak, E.T.; Poulsen, F.M.; Dobson, C.M. Proton nuclear overhauser effects and protein dynamics. J. Am. Chem. Soc., 1981, 103(22), 6574-6580.
[http://dx.doi.org/10.1021/ja00412a007]
[106]
Torda, A.E.; Norton, R.S. Proton nmr relaxation study of the dynamics of anthopleurin-A in solution. Biopolymers, 1989, 28(3), 703-716.
[http://dx.doi.org/10.1002/bip.360280303] [PMID: 2706310]
[107]
kay, L.E.; Muhandiram, D.R.; Wolf, G.; Shoelson, S.E.; Forman-Kay, J.D. Correlation between binding and dynamics at SH2 domain interfaces. Nat. Struct. Biol., 1998, 5(2), 156-163.
[http://dx.doi.org/10.1038/nsb0298-156] [PMID: 9461082]
[108]
Morris, G.A.; Freeman, R. Enhancement of nuclear magnetic resonance signals by polarization transfer. J. Am. Chem. Soc., 1979, 101(3), 760-762.
[http://dx.doi.org/10.1021/ja00497a058]
[109]
Doddrell, D.M.; Pegg, D.T.; Bendall, M.R.; Doddrell, D.M.; Pegg, D.T.; Bendall, M.R. Distortionless enhancement of NMR signals by polarization transfer. J. Magn. Reson., 1982, 48(2), 323-327.
[http://dx.doi.org/10.1016/0022-2364(82)90286-4]
[110]
Carr, H.Y.; Purcell, E.M. Effects of diffusion on free precession in nuclear magnetic resonance experiments. Phys. Rev., 1954, 94(3), 630-638.
[http://dx.doi.org/10.1103/PhysRev.94.630]
[111]
Meiboom, S.; Gill, D. Modified spin‐echo method for measuring nuclear relaxation times. Rev. Sci. Instrum., 1958, 29(8), 688-691.
[http://dx.doi.org/10.1063/1.1716296]
[112]
Noggle, J.H.R.E.S. The Nuclear Overhauser Effect: Chemical Applications; Academic Press: New York, 1971.
[113]
Fesik, S.W.; Zuiderweg, E.R.P. Heteronuclear three-dimensional NMR spectroscopy of isotopically labelled biological macromolecules. Q. Rev. Biophys., 1990, 23(2), 97-131.
[http://dx.doi.org/10.1017/S0033583500005515] [PMID: 2188281]
[114]
Nonoyama, A.; Laurence, J.S.; Garriques, L.; Qi, H.; Le, T.; Middaugh, C.R. A biophysical characterization of the peptide drug pramlintide (AC137) using empirical phase diagrams. J. Pharm. Sci., 2008, 97(7), 2552-2567.
[http://dx.doi.org/10.1002/jps.21197] [PMID: 17879973]
[115]
King, M.V. A low-resolution structural model for cubic glucagon based on packing of cylinders. J. Mol. Biol., 1965, 11(3), 549-IN5.
[http://dx.doi.org/10.1016/S0022-2836(65)80010-9] [PMID: 14267276]
[116]
Sasaki, K.; Dockerill, S.; Adamiak, D.A.; Tickle, I.J.; Blundell, T. X-ray analysis of glucagon and its relationship to receptor binding. Nature, 1975, 257(5529), 751-757.
[http://dx.doi.org/10.1038/257751a0] [PMID: 171582]
[117]
Swann, J.C.; Hammes, G.G. Self-association of glucagon, Equilibrium studies. Biochemistry, 1969, 8(1), 1-7.
[http://dx.doi.org/10.1021/bi00829a001] [PMID: 5777323]
[118]
Gratzer, W.B.; Creeth, J.M.; Beaven, G.H. Presence ot trimers in glucagon solution. Eur. J. Biochem., 1972, 31(3), 505-509.
[http://dx.doi.org/10.1111/j.1432-1033.1972.tb02558.x] [PMID: 4650155]
[119]
Andersen, C.B.; Otzen, D.; Christiansen, G.; Rischel, C. Glucagon amyloid-like fibril morphology is selected via morphology-dependent growth inhibition. Biochemistry, 2007, 46(24), 7314-7324.
[http://dx.doi.org/10.1021/bi6025374] [PMID: 17523599]
[120]
Beaven, G.H.; Gratzer, W.B.; Davies, H.G. Formation and structure of gels and fibrils from glucagon. Eur. J. Biochem., 1969, 11(1), 37-42.
[http://dx.doi.org/10.1111/j.1432-1033.1969.tb00735.x] [PMID: 5353602]
[121]
Moran, E.C.; Chou, P.Y.; Fasman, G.D. Conformational transitions of glucagon in solution: The α → β transition. Biochem. Biophys. Res. Commun., 1977, 77(4), 1300-1306.
[http://dx.doi.org/10.1016/S0006-291X(77)80121-6] [PMID: 20100]
[122]
Pedersen, J.S. The nature of amyloid-like glucagon fibrils. J. Diabetes Sci. Technol., 2010, 4(6), 1357-1367.
[http://dx.doi.org/10.1177/193229681000400609] [PMID: 21129330]
[123]
Hudson, F.M.; Andersen, N.H. Exenatide: NMR/CD evaluation of the medium dependence of conformation and aggregation state. Biopolymers, 2004, 76(4), 298-308.
[http://dx.doi.org/10.1002/bip.20126] [PMID: 15386269]
[124]
Benet, A.; Halseth, T.; Kang, J.; Kim, A.; Ackermann, R.; Srinivasan, S.; Schwendeman, S.; Schwendeman, A. The Effects of pH and excipients on exenatide stability in solution. Pharmaceutics, 2021, 13(8), 1263.
[http://dx.doi.org/10.3390/pharmaceutics13081263] [PMID: 34452224]
[125]
Food and Drug Administration. ANDAs for certain highly purified synthetic peptide drug products that refer to listed drugs of rDNA origin; , 2018. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/andas-certain-highly-purified-synthetic-peptide-drug-products-refer-listed-drugs-rdna-origin
[126]
Kamerzell, T.J.; Esfandiary, R.; Joshi, S.B.; Middaugh, C.R.; Volkin, D.B. Protein-excipient interactions: Mechanisms and biophysical characterization applied to protein formulation development. Adv. Drug Deliv. Rev., 2011, 63(13), 1118-1159.
[http://dx.doi.org/10.1016/j.addr.2011.07.006] [PMID: 21855584]
[127]
Teeters, M.; Bezila, D.; Benner, T.; Alfonso, P.; Alred, P. Predicting diafiltration solution compositions for final ultrafiltration/diafiltration steps of monoclonal antibodies. Biotechnol. Bioeng., 2011, 108(6), 1338-1346.
[http://dx.doi.org/10.1002/bit.23067] [PMID: 21328314]
[128]
Stoner, M.R.; Fischer, N.; Nixon, L.; Buckel, S.; Benke, M.; Austin, F.; Randolph, T.W.; Kendrick, B.S. Protein−solute interactions affect the outcome of ultrafiltration/diafiltration operations. J. Pharm. Sci., 2004, 93(9), 2332-2342.
[http://dx.doi.org/10.1002/jps.20145] [PMID: 15295793]
[129]
Konarkowska, B.; Aitken, J.F.; Kistler, J.; Zhang, S.; Cooper, G.J.S. The aggregation potential of human amylin determines its cytotoxicity towards islet β-cells. FEBS J., 2006, 273(15), 3614-3624.
[http://dx.doi.org/10.1111/j.1742-4658.2006.05367.x] [PMID: 16884500]
[130]
Elgersma, R.C.; Meijneke, T.; Posthuma, G.; Rijkers, D.T.S.; Liskamp, R.M.J. Self-assembly of amylin(20-29) amide-bond derivatives into helical ribbons and peptide nanotubes rather than fibrils. Chemistry, 2006, 12(14), 3714-3725.
[http://dx.doi.org/10.1002/chem.200501374] [PMID: 16528792]
[131]
Maggio, E.T. Therapeutics, A. use of excipients to control aggregation in peptide and protein formulations use of excipients to control aggregation in peptide and protein formulations. J. Excipients. Food Chem., 2010, 1(2), 40-49.
[132]
Indrakumar, S.; Zalar, M.; Tschammer, N.; Pohl, C.; Nørgaard, A.; Streicher, W.; Harris, P.; Golovanov, A.P.; Peters, G.H.J. Development of a fast screening method for selecting excipients in formulations using MD simulations, NMR and microscale thermophoresis. Eur. J. Pharm. Biopharm., 2021, 158, 11-20.
[http://dx.doi.org/10.1016/j.ejpb.2020.10.015] [PMID: 33137420]
[133]
Evers, A.; Bossart, M.; Pfeiffer-Marek, S.; Elvert, R.; Schreuder, H.; Kurz, M.; Stengelin, S.; Lorenz, M.; Herling, A.; Konkar, A.; Lukasczyk, U.; Pfenninger, A.; Lorenz, K.; Haack, T.; Kadereit, D.; Wagner, M. Dual Glucagon-like Peptide 1 (GLP-1)/Glucagon receptor agonists specifically optimized for multidose formulations. J. Med. Chem., 2018, 61(13), 5580-5593.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00292] [PMID: 29879354]
[134]
Evers, A.; Pfeiffer-Marek, S.; Bossart, M.; Heubel, C.; Stock, U.; Tiwari, G.; Gebauer, B.; Elshorst, B.; Pfenninger, A.; Lukasczyk, U.; Hessler, G.; Kamm, W.; Wagner, M. Peptide optimization at the drug discovery-development interface: Tailoring of physicochemical properties toward specific formulation requirements. J. Pharm. Sci., 2019, 108(4), 1404-1414.
[http://dx.doi.org/10.1016/j.xphs.2018.11.043] [PMID: 30528197]
[135]
D’Addio, S.M.; Su, Y.; Yin, D.; Zhang, J.; Kemp, E.; Gindy, M.E. Antimicrobial excipient-induced reversible association of therapeutic peptides in parenteral formulations. J. Pharm. Sci., 2020, 1-10.
[http://dx.doi.org/10.1016/j.xphs.2020.09.027] [PMID: 32980392]
[136]
Poppe, L.; Knutson, N.; Cao, S.; Wikström, M. In situ quantification of polysorbate in pharmaceutical samples of therapeutic proteins by hydrodynamic profiling by NMR spectroscopy. Anal. Chem., 2019, 91(12), 7807-7811.
[http://dx.doi.org/10.1021/acs.analchem.9b01442] [PMID: 31117409]
[137]
Bramham, J.E.; Podmore, A.; Davies, S.A.; Golovanov, A.P. Comprehensive assessment of protein and excipient stability in biopharmaceutical formulations using 1 H NMR spectroscopy. ACS Pharmacol. Transl. Sci., 2021, 4(1), 288-295.
[http://dx.doi.org/10.1021/acsptsci.0c00188] [PMID: 33659867]
[138]
Williamson, M.P. Using chemical shift perturbation to characterise ligand binding. Prog. Nucl. Magn. Reson. Spectrosc., 2013, 73, 1-16.
[http://dx.doi.org/10.1016/j.pnmrs.2013.02.001] [PMID: 23962882]
[139]
Pandya, A.; Howard, M.J.; Zloh, M.; Dalby, P.A. An evaluation of the potential of NMR spectroscopy and computational modelling methods to inform biopharmaceutical formulations. Pharmaceutics, 2018, 10(4), 1-24.
[http://dx.doi.org/10.3390/pharmaceutics10040165]
[140]
Malmodin, D.; Pedersen, A.; Karlsson, B.G.; Forsander, G. NMR spectroscopic analysis to evaluate the quality of insulin: Concentration, variability, and excipient content. J. Diabetes Sci. Technol., 2020, 14(1), 180-184.
[http://dx.doi.org/10.1177/1932296819831995] [PMID: 30782004]
[141]
Akoka, S.; Barantin, L.; Trierweiler, M. Concentration measurement by proton NMR using the ERETIC method. Anal. Chem., 1999, 71(13), 2554-2557.
[http://dx.doi.org/10.1021/ac981422i] [PMID: 21662801]
[142]
Falk, B.T.; Liang, Y.; McCoy, M.A. Profiling insulin oligomeric states by 1H NMR spectroscopy for formulation development of ultra-rapid-acting insulin. J. Pharm. Sci., 2020, 109(1), 922-926.
[http://dx.doi.org/10.1016/j.xphs.2019.07.025] [PMID: 31449814]
[143]
FDA. Application to marketa new or abbreviated new drug or biologic for human use (Title 21, Code of Federal Regulations, Parts 314 & 601). 2020, 0910, 4-6.
[144]
Li, C.H.; Nguyen, X.; Narhi, L.; Chemmalil, L.; Towers, E.; Muzammil, S.; Gabrielson, J.; Jiang, Y. Applications of Circular Dichroism (CD) for structural analysis of proteins: Qualification of near‐ and far‐UV CD for protein higher order structural analysis. J. Pharm. Sci., 2011, 100(11), 4642-4654.
[http://dx.doi.org/10.1002/jps.22695] [PMID: 21732370]
[145]
Kelly, S.; Price, N. The use of circular dichroism in the investigation of protein structure and function. Curr. Protein Pept. Sci., 2000, 1(4), 349-384.
[http://dx.doi.org/10.2174/1389203003381315] [PMID: 12369905]
[146]
Wu, L.; Smith, H.H.Z.; Ng, Y.X.L. Drug Product Approval in the United States and International Harmonization, 2nd ed; Academic Press, 2017, pp. 1049-1077.
[147]
Wu, L.C.; Chen, F.; Lee, S.L.; Raw, A.; Yu, L.X. Building parity between brand and generic peptide products: Regulatory and scientific considerations for quality of synthetic peptides. Int. J. Pharm., 2017, 518(1-2), 320-334.
[http://dx.doi.org/10.1016/j.ijpharm.2016.12.051] [PMID: 28027918]
[148]
Wu, L. Regulatory Considerations for Peptide Therapeutics.In: Peptide Therapeutics: Strategy and Tactics for Chemistry, Manufacturing, and Controls; Royal Society of Chemistry, 2019, pp. 1-30.
[http://dx.doi.org/10.1039/9781788016445-00001]
[149]
Wishart, D.S.; Bigam, C.G.; Holm, A.; Hodges, R.S.; Sykes, B.D. 1H, 13C and 15N random coil NMR chemical shifts of the common amino acids. I. Investigations of nearest-neighbor effects. J. Biomol. NMR, 1995, 5(1), 67-81.
[http://dx.doi.org/10.1007/BF00227471] [PMID: 7881273]
[150]
Schwarzinger, S.; Kroon, G.J.A.; Foss, T.R.; Chung, J.; Wright, P.E.; Dyson, H.J. Sequence-dependent correction of random coil NMR chemical shifts. J. Am. Chem. Soc., 2001, 123(13), 2970-2978.
[http://dx.doi.org/10.1021/ja003760i] [PMID: 11457007]
[151]
Braun, D.; Wider, G.; Wuethrich, K. Sequence-corrected 15N “random coil” chemical shifts. J. Am. Chem. Soc., 1994, 116(19), 8466-8469.
[http://dx.doi.org/10.1021/ja00098a005]
[152]
Martinez Morales, M.; Zalar, M.; Sonzini, S.; Golovanov, A.P.; van der Walle, C.F.; Derrick, J.P. Interaction of a macrocycle with an aggregation-prone region of a monoclonal antibody. Mol. Pharm., 2019, 16(7), 3100-3108.
[http://dx.doi.org/10.1021/acs.molpharmaceut.9b00338] [PMID: 31088082]
[153]
Zalar, M.; Svilenov, H.L.; Golovanov, A.P. Binding of excipients is a poor predictor for aggregation kinetics of biopharmaceutical proteins. Eur. J. Pharm. Biopharm., 2020, 151, 127-136.
[http://dx.doi.org/10.1016/j.ejpb.2020.04.002] [PMID: 32283214]
[154]
Brinson, R.G.; Marino, J.P.; Delaglio, F.; Arbogast, L.W.; Evans, R.M.; Kearsley, A.; Gingras, G.; Ghasriani, H.; Aubin, Y.; Pierens, G.K.; Jia, X.; Mobli, M.; Grant, H.G.; Keizer, D.W.; Schweimer, K.; Ståhle, J.; Widmalm, G.; Zartler, E.R.; Lawrence, C.W.; Reardon, P.N.; Cort, J.R.; Xu, P.; Ni, F.; Yanaka, S.; Kato, K.; Parnham, S.R.; Tsao, D.; Blomgren, A.; Rundlöf, T.; Trieloff, N.; Schmieder, P.; Ross, A.; Skidmore, K.; Chen, K.; Keire, D.; Freedberg, D.I.; Suter-Stahel, T.; Wider, G.; Ilc, G.; Plavec, J.; Bradley, S.A.; Baldisseri, D.M.; Sforça, M.L.; Zeri, A.C.M.; Wei, J.Y.; Szabo, C.M.; Amezcua, C.A.; Jordan, J.B.; Wikström, M. Enabling adoption of 2D-NMR for the higher order structure assessment of monoclonal antibody therapeutics. Mabs, 2019, 11(1), 94-105.
[http://dx.doi.org/10.1080/19420862.2018.1544454] [PMID: 30570405]
[155]
Falk, B.T.; Liang, Y.; Bailly, M.; Raoufi, F.; Kekec, A.; Pissarnitski, D.; Feng, D.; Yan, L.; Lin, S.; Fayadat-Dilman, L.; McCoy, M.A. NMR assessment of therapeutic peptides and proteins: Correlations that reveal interactions and motions. ChemBioChem, 2020, 21(3), 315-319.
[http://dx.doi.org/10.1002/cbic.201900296] [PMID: 31283075]
[156]
Poppe, L.; Jordan, J.B.; Lawson, K.; Jerums, M.; Apostol, I.; Schnier, P.D. Profiling formulated monoclonal antibodies by (1)H NMR spectroscopy. Anal. Chem., 2013, 85(20), 9623-9629.
[http://dx.doi.org/10.1021/ac401867f] [PMID: 24006877]
[157]
Arbogast, L.W.; Brinson, R.G.; Marino, J.P. Application of natural isotopic abundance 1H-13C- and 1H-15N-correlated two-dimensional NMR for evaluation of the structure of protein therapeutics. Methods Enzymol., 2016, 566, 3-34.
[http://dx.doi.org/10.1016/bs.mie.2015.09.037] [PMID: 26791974]
[158]
Falk, B.T.; Liang, Y.; McCoy, M.A. Diffusion profiling of therapeutic proteins by using solution NMR spectroscopy. ChemBioChem, 2019, 20(7), 896-899.
[http://dx.doi.org/10.1002/cbic.201800631] [PMID: 30515922]