Peptides Targeting G-Quadruplex Structures

Abstract

Research in recent decades has revealed that some DNA and RNA secondary structures modulate a variety of cellular events. One secondary structure, the Guanine(G)-quadruplex, also regulates various cellular events that are mostly related to serious diseases. Systems capable of controlling DNA and RNA G-quadruplex structures would therefore be useful for the modulation of various cellular events to produce biological effects. Because of their biological importance, many G-quadruplex-targeting compounds have been described. However, the next generation of targeting molecules should exhibit increased G-quadruplex sequence specificity, a higher structure-inducing or -collapsing ability, and a greater degree of functionality, including on–off switches of binding ability and cellular penetration. Peptides might be good candidates for these next-generation G-quadruplex-targeting molecules due to the following advantages: (1) their easy design and synthesis, (2) their ability to mimic protein–G-quadruplex interactions, (3) the possibility of employing artificial amino acids in addition to naturally occurring amino acids, and (4) the ability to combine G-quadruplex-binding sequences with other functional sequences. Accordingly, several peptide-based compounds, such as furan-based cyclic peptides, PNA-conjugated peptides, and small molecule-peptide conjugates, have been developed. In this chapter, we introduce all these peptide ligands and describe most of the approaches for targeting G-quadruplex structures. We then conclude that peptides are among the most promising functional ligands for G-quadruplexes to control various biological events in next-generation approaches.