The article by Dr. Michael D. Heagy and Dr. Susantha K.
Ganegamage is published in the journal, Current Organic Chemistry, 2022
8-DEC-2022
DNA,
the genetic material compacted in chromosomes, stores information to regulate
all the cell processes in the body. Two decades ago, in addition to the widely
known Watson-Crick double helix model of DNA, scientists postulated an
alternative conformation that controls different biological functions. This
conformation was named G-Quadruplex as it contains a high guanine-rich sequence
of DNA strands arranging four Guanine structures in a planar conformation stack
on each other. This stable structure is responsible for crucial biological
processes, including regulation of genes, cell division, aging, cell death,
etc. Irregularities in gene regulation cause globally crucial human health
issues like cancer. Due to the frequency of localization of guanidine-rich DNA
sequences, computational calculations have predicted that the human genome
contains approximately 376,000 potential putative G-quadruplex forming
sequences, mainly at the end of the chromosome called telomeres. Around 20,000
sites are associated with oncogenes in which the gene regulates cancer development
and progression. The biological role of the G-quadruplex in cancer prognosis
and pathogenesis has not been fully understood by molecular biologists due to a
lack of adequate visualization or tracking methods for studying molecules in a
complex biological matrix. Therefore, developing G-quadruplex-selective probes
is an essential but challenging task for molecular therapeutic, diagnostic,
imaging, and sensing applications.
The
G-Quadruplex structures can exist in various conformations or forms called topologies.
The relatively overwhelming amount of double standard DNA, its dynamic nature,
and polymorphism make it even more challenging to detect in a real-time
environment. Initially, researchers adapted conventional methods such as
platinum crosslinking, FRET, I-radio probing, covalent ligation, click
reaction, sedimentation, and small molecule probes. Among them,
fluorescence-active small molecule investigation is the more direct, emerging,
and real-time visualization method. Over the past two and a half decades,
researchers have developed fluorescence-active small molecular probes for
G-Quadruplex detection. They evaluated their selectivity of recognition over
duplex DNA in mechanical parameters such as binding affinity, absorbance, and
fluorescence enhancement or quenching and fluorescence lifetime change upon
binding with G-quadruplexes. The research involved evaluating various
fluorescence cores with different side chains or binders, increasing the
selectivity towards the G-Quadruplex over the duplex DNA. The
structure-activity relationship study of the probes has helped the discovery of
superior probes with ideal characteristics.
In
this review, Michael Heagy and Susantha K. Ganegamage present a comprehensive
study of probes developed over the last two and a half decades. The researchers
have classified and summarized several classes of probes, including
carbocyanine, porphyrins, ethidium, carbazoles, acridines, tripodal or
tetrapodal probes, pyrimidine carboxamides, triangulenium, anthraquinones, polyaromatic
hydrocarbons, BODIPY dyes, berberines, acetones and their derivatives for the
variation of selectivity, photophysical, and biological properties concerning
the structural modifications. “The intent of this exhaustive review is to
provide helpful guidance and insights for designing novel fluorescent DNA
probes with optimal characteristics,” says Professor Heagy who heads the
Department of Chemistry and Materials Science, at the Rochester Institute of
Technology. The review is published in Current Organic
Chemistry.
To
access the research, please visit: https://www.eurekaselect.com/article/125423
Current Organic Chemistry
10.2174/1385272826666220811102939
Illuminating the G-Quadruplex: A Review on Fluorescent
Probes for Detecting Polymorphic G-Quartet DNA Structures
12-Sep-2022
