Title
Second Generation G-Quadruplex Stabilizing Trimethine Cyanines
Author
Eric A. Owens, Hang T. Huynh, Ekaterina M. Stroeva, Arghya Barman, Kostiantyn Ziabrev, Ananya Paul, Sarah V. Nguyen, Matthew Laramie, Donald Hamelberg, Markus W. Germann, W. David Wilson, Maged Henary
Year
2019
Journal
Bioconjugate Chemistry
Abstract
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.
Instrument
J-810
Keywords
Circular dichroism, Induced circular dichroism, Ligand binding, DNA structure, G-quadruplex structure, Biochemistry