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Single-molecule Manipulation of G-quadruplexes by Magnetic Tweezers
Published on: September 19, 2017
Design, synthesis and evaluation of 4,7-diamino-1,10-phenanthroline G-quadruplex ligands
Mads Corvinius Nielsen1, Jonas Borch, Trond Ulven
1Department of Physics and Chemistry, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
Abstract:
A series of 4,7-diamino-1,10-phenanthroline derivatives carrying positively charged side chains has been synthesized, and their G-quadruplex interaction evaluated by circular dichroism (CD) and surface plasmon resonance (SPR). In absence of side chains, 4,7-diamino-1,10-phenanthroline exhibits a weak but significant G-quadruplex stabilizing effect, compared to no stabilization by 1,10-phenanthroline. We hypothesize that this effect is due to increased basicity of the phenanthroline nitrogens and protonation or ion chelation to form a central positive charge which stack on the G-tetrad above the central ionic column. Introduction of positively charged side chains results in compounds with appreciable G-quadruplex stabilizing properties and high aqueous solubility, with the longer side chains giving more potent compounds. Ligands carrying guanidine side chains in general show higher quadruplex stabilizing activity and distinctly slower kinetic properties than their amino and dimethylamino analogues, possibly due to specific hydrogen bond interactions with the G-quadruplex loops.
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