Probing protein geranylgeranylation: Development of GGPP analog SAR to selectively target GGTase I
Abstract
The initial goal of this project is to deepen the understanding of GGTase I substrate specificity with regards to both prenyl and protein substrates. The over-arching goal is the development of biologically useful isoprenoid tools for the modification of CaaX proteins. This dissertation focuses on the synthesis of a small library of GGPP analogs, evaluation of GGPP analogs against peptide substrate libraries, and the development of two prenylation prodrug inhibitors. We have established that GGPP analogs can significantly alter the peptide substrate specificity of GGTase I and we have identified a unique GGPP-derived GGTase I inhibitor, with intriguing biological activity.
Degree
Ph.D.
Advisors
Gibbs, Purdue University.
Subject Area
Biochemistry
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