DNA G-Quadruplexes and I-Motifs in Therapeutics and Diagnostics

Abstract

G-quadruplex- and i-motif-based DNA oligomers are being investigated for their integration into therapeutic and diagnostic micro-assemblies. Examples include quadruplex-forming aptamers as potential anti-HIV agents, and serum-stable quadruplexes as carriers for delivering porphyrins into cancer cells for photodynamic therapy. The i-motifs from C-rich DNA find application in pH-triggered hydrogels that can carry agents like drugs, proteins, and polymers to their targets. The pH-dependent conformational dynamics of i-motifs also make them useful as biosensors for detecting pH changes in cellular microenvironments. Due to these and many other applications, and in an effort to present a compendia of recent uses of quadruplexes and i-motifs, this chapter will concern itself with formation of G-quadruplexes and i-motifs; their physical and chemical properties; the effects of molecular crowding and hydration on their structure and stability; and their application in therapeutics as drug targets, drug-delivery vehicles, and diagnostic tools.