A new family of small molecules to probe the reactivation of mutant p53

ORGN 434

Jaclyn A. Iera, Department of Chemistry; Laboratory of Bioorganic Chemistry, NIDDK, DHHS, Northwestern University; National Institute of Health, 9000 Rockville Pike, Bldg 8A Rm 1A25, Bethesda, MD 20892, Gerard P. Zambetti, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN 38105, and Daniel H. Appella, Laboratory of Bioorganic Chemistry, NIDDK, DHHS, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892.
The protein p53 is an important tumor suppressor that, in damaged cells causes cell cycle arrest or apoptosis. A mutated form of p53, which is inactive, is found in approximately 50% of human tumor cells. Small molecules that can restore the natural tumor suppressor functions to the protein, possibly via reactivation of mutant p53, could become important chemotherapeutic agents. Our research in p53 restoration focuses on developing a synthetically accessible class of molecules that can be easily modified to examine structural activity relationships (SAR), mechanism of reactivation, or to optimize for anticancer activity. We have identified several serine derived small molecules, which were able to reactivate mutant p53 and recognized certain functionalities within key sites that may be critical for reactivation of mutant p53. An ELISA is currently being developed for an efficient method to test the activities of compounds within a library.
 

Bioorganic, Metal-Mediated Reactions, and Molecular Recognition
8:00 PM-10:00 PM, Tuesday, 30 August 2005 Washington DC Convention Center -- Hall A, Poster

Division of Organic Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005