The protein p53 is recognized as one of the most important guardians in the body that prevents tumor development. Since its discovery, the roles of p53 have been the focus of research geared toward understanding the mechanisms of uncontrolled cell growth or cancer. Specifically, when healthy cells are damaged, p53 levels increase, followed by inhibition of cell growth or programmed cell death. This regulation of damaged cells is initiated by a p53-DNA binding event. Mutated forms of p53 that lose the ability to bind DNA can not arrest cell growth, and the proliferation of damaged cells results. Mutant forms of p53 are present in approximately 50% of all human cancers. If mutant p53 can be induced to readopt the active form of wild-type p53, tumor suppressor function can be restored. Molecules that reactivate mutant p53 could selectively target tumor cells due to the accumulation of mutated p53 in these cells. In our research, we are developing a unique class of molecules to reactivate mutant p53 associated with cancer. We have developed a synthetically accessible class of molecules that can be easily modified to examine structural activity relationships, mechanism of biological activity, or optimize for anticancer activity, and we are currently examining the activity of these molecules in a variety of cancer cell lines.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Intramural Research (Z01)
Project #
1Z01DK031123-01
Application #
7197173
Study Section
(LBC)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2005
Total Cost
Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Pokorski, Jonathan K; Jenkins, Lisa M Miller; Feng, Hanqiao et al. (2007) Introduction of a triazole amino acid into a peptoid oligomer induces turn formation in aqueous solution. Org Lett 9:2381-3
Hara, Toshiaki; Durell, Stewart R; Myers, Michael C et al. (2006) Probing the structural requirements of peptoids that inhibit HDM2-p53 interactions. J Am Chem Soc 128:1995-2004
Myers, Michael C; Wang, Jinling; Iera, Jaclyn A et al. (2005) A new family of small molecules to probe the reactivation of mutant p53. J Am Chem Soc 127:6152-3