G-quadruplex binding assays and compounds therefor

摘要

The present invention provides methods for assaying binding of compounds to G-quadruplex structures. Also provided are methods for screening candidate compounds for use as modulators of G-quadruplex activity, and methods for screening candidate compounds for telomerase inhibitory activity. The invention further provides novel compounds useful in the assays of the invention.

主权项

1. A method for determining the binding affinity of a candidate compound for G-quadruplex structures comprising the steps of:
(a) providing a G-quadruplex polynucleotide analog, said G-quadruplex polynucleotide analog having a G-quadruplex structure and at least one intrinsic fluorescent moiety; (b) contacting said G-quadruplex polynucleotide analog with said candidate compound; (c) measuring a difference in a fluorescence property of said G-quadruplex polynucleotide analog; and (d) determining the binding affinity of the candidate compound; wherein the G-quadruplex analog polynucleotide comprises: a nucleobase sequence that is an analog of a telomeric repeat sequence; and at least one nucleotide comprising a 6-methyl-isoxanthopterin nucleobase;wherein:
said G-quadruplex analog polynucleotide forms a G-quadruplex structure; and each 6-methyl-isoxanthopterin nucleobase is located within said G-quadruplex structure.