The 3-dimensional structure of anticancer drug-DNA complexes determined by X-ray crystallography

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/107228

Funding Status
Closed

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Funded Activity Summary

Our main objective is to discover the molecular details of how cancer drugs interact with DNA and how these interactions differ from those of inactive chemically related compounds. We propose to use X-ray crystallography together with the successful methods we have developed for determining the 3-dimensional structures of the DNA complexes of a class of antitumour active drugs to study the complexes of other clinically or scientifically important DNA intercalating anticancer drugs. These agents act by poisoning the DNA binding enzyme topoisomerase. Crystallographic analysis will give us unequivocal answers at the atomic level as to the exact way in which the drug binds to DNA and how this binding differs between antitumour active and inactive compounds. We believe that a knowledge of the DNA binding mode of a class of intercalating anticancer drugs at the atomic level is valuable in guiding drug design within that class.

Funded Activity Details

Start Date: 01-01-2000

End Date: 01-01-2002

Funding Scheme: NHMRC Project Grants

Funding Amount: $264,358.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Oncology And Carcinogenesis

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

3-dimensional structures | X-ray crystallography | anticancer drug-DNA complexes | anticancer drugs | cancer | chemotherapy | topoisomerase poisons

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