A comparison of palindrome and pseudopalindrome cutters

Abstract

Structural investigations into quadruplexes, formed from guanine rich sequences found in the human chromosome, and development of small molecule ligands that can stabilize these structures have been the main focus of our research. The targeting of the telomere, a G-rich hexanucleotide repeat sequence TAGGGT, found at the end of all mammalian chromosomes has lead to the development of a series of ligands that can effectively inhibit the enzyme telomerase. Critically a 3’ single stranded overhang, located at the end of the chromosome, is the substrate for the ribonucleoprotein telomerase. Folding of these telomeric repeats into higher order DNA structures inhibits access of telomerase and prevents telomere maintenance. Additionally, the binding of other associated proteins that form part of the telosome, are also disrupted leading rapidly to chromosomal damage, such as chromosomal fusions and apoptosis.Wewill discuss our research into the folding topologies that are available to these telomeric sequences and other target sequence found in the chromosome, and the design of selective ligands that target these novel topologies. This is of particular importance with the identification of quanine rich sequences that have been shown to form stable quadruplex structures within promotor regions of onogenes. The structural diversity of the quadruplex structures formed from these G-rich DNA sequences will also be reviewed. m04.o03