DNA Tetraplex-Binding Drugs  Structure-Selective Targeting is Critical for Antitumour Telomerase Inhibition

Philip   J.   Perry; Terence   C.   Jenkins

Abstract

Four-stranded tetraplex (“G-quadruplex”) DNA represents a new paradigm for the design of DNA-interactive antitumour drugs, as the formed DNA-drug complexes have been suggested to interfere with critical telomerase function. The unique structural features presented by tetraplex over duplex DNA have stimulated the design of small ligand molecules able to selectively promote the formation and-or stabilisation of such higher-order DNA structures. Current developments in tetraplex-targeted telomerase inhibitors, and importantly their DNA structural selectivity, are explored.

Keywords: DNA Tetraplex, Antitumour Telomerase, nucleic acid biotargets, malignant transformation, covalent fixation processes, chemotherapeutic target, Guanine rich, telomerase activity, isothermal titration calorimetry, stacked G tetrads, mesoporphyrin NMM dye