The protein 'Smac' (or Smac/Diablo) plays an important role in programmed cell death, (apoptosis) by down regulating the inhibitor of apoptosis (lAP) proteins, which are overexpressed in many cancers. ? ? The proposed studies first examine how Smac is mobilized within the death pathway under various death stimuli. Furthermore, we explore the utility of Smac small molecule peptide mimics for use in diagnostic imaging of cancers via novel molecular targeting. We also explore the use of Smac mimetics as general, small molecule as anticancer agents to avert, or kill tumor cells. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM059348-06
Application #
7115799
Study Section
Physical Biochemistry Study Section (PB)
Program Officer
Preusch, Peter C
Project Start
2000-02-01
Project End
2007-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
6
Fiscal Year
2006
Total Cost
$273,673
Indirect Cost
Name
Duke University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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Wist, Aislyn D; Gu, Lichuan; Riedl, Stefan J et al. (2007) Structure-activity based study of the Smac-binding pocket within the BIR3 domain of XIAP. Bioorg Med Chem 15:2935-43
Springs, Stacy L; Diavolitsis, Virginia M; Goodhouse, Joseph et al. (2002) The kinetics of translocation of Smac/DIABLO from the mitochondria to the cytosol in HeLa cells. J Biol Chem 277:45715-8
Kipp, Rachael A; Case, Martin A; Wist, Aislyn D et al. (2002) Molecular targeting of inhibitor of apoptosis proteins based on small molecule mimics of natural binding partners. Biochemistry 41:7344-9
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