title: A highly potent and selective PKCalpha inhibitor generated via combinatorial modification of a peptide scaffold.
abstract: A potent and highly selective inhibitor of protein kinase C alpha has been generated via the combinatorial modification of a consensus sequence peptide. The inhibitor displays a Ki of 800 pM versus variable peptide substrate and good selectivity versus other members of the PKC family, including PKCbeta (385-fold), PKCgamma (580-fold), PKCdelta (2730-fold), PKCepsilon (600-fold), PKCeta (1310-fold), PKCtheta (1210-fold), PKCiota (940-fold), and PKCzeta (640-fold). The parallel synthesis strategy employed is easily automated and straightforward to implement.
authors.affiliation: The Albert Einstein College of Medicine, Department of Biochemistry, 1300 Morris Park Ave., Bronx, New York 10461, USA.
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Sandip K
authors.initials: SK
authors.lastname: Nandy
authors.forename: David S
authors.initials: DS
authors.lastname: Lawrence
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000494:pharmacology; D001667:Binding, Competitive; D020650:Combinatorial Chemistry Techniques; D016384:Consensus Sequence; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051571:Protein Kinase C-alpha; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D010455:Peptides; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha