Open AccessSecond Generation G-Quadruplex Stabilizing Trimethine Cyanines
Author(s) -
Eric A. Owens,
Hang T. Huynh,
Ekaterina Stroeva,
Arghya Barman,
Kostiantyn Ziabrev,
A. Paul,
Sarah V. Nguyen,
Matthew Laramie,
Donald Hamelberg,
Markus W. Germann,
W. David Wilson,
Maged Henary
Publication year - 2019
Publication title -
bioconjugate chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.279
H-Index - 172
eISSN - 1520-4812
pISSN - 1043-1802
DOI - 10.1021/acs.bioconjchem.9b00571
Subject(s) - chemistry , cyanine , stacking , g quadruplex , dna , duplex (building) , biophysics , combinatorial chemistry , stereochemistry , biochemistry , organic chemistry , physics , quantum mechanics , fluorescence , biology
G-Quadruplex DNA has been recognized as a highly appealing target for the development of new selective chemotherapeutics, which could result in markedly reduced toxicity toward normal cells. In particular, the cyanine dyes that bind selectively to G-quadruplex structures without targeting duplex DNA have attracted attention due to their high amenability to structural modifications that allows fine-tuning of their biomolecular interactions. We have previously reported pentamethine and symmetric trimethine cyanines designed to effectively bind G-quadruplexes through end stacking interactions. Herein, we are reporting a second generation of drug candidates, the asymmetric trimethine cyanines. These have been synthesized and evaluated for their quadruplex binding properties. Incorporating a benz[ c , d ]indolenine heterocyclic unit increased overall quadruplex binding, and elongating the alkyl length increases the quadruplex-to-duplex binding specificity.