Medicine and Health Sciences Commons^™

Identification Of Protein Palmitoylation Inhibitors From A Scaffold Ranking Library, Laura D. Hamel, Brian J. Lenhart, David A. Mitchell, Radleigh Santos, Marc A. Giulianotti, Robert J. Deschenes

Mathematics Faculty Articles

The addition of palmitoyl moieties to proteins regulates their membrane targeting, subcellular localization, and stability. Dysregulation of the enzymes which catalyzed the palmitoyl addition and/or the substrates of these enzymes have been linked to cancer, cardiovascular, and neurological disorders, implying these enzymes and substrates are valid targets for pharmaceutical intervention. However, current chemical modulators of zDHHC PAT enzymes lack specificity and affinity, underscoring the need for screening campaigns to identify new specific, high affinity modulators. This report describes a mixture based screening approach to identify inhibitors of Erf2 activity. Erf2 is the Saccharomyces cerevisiae PAT responsible for catalyzing the palmitoylation …