A highly potent and selective PKCalpha inhibitor generated via combinatorial modification of a peptide scaffold.
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.
Lee
Jung Hwan
JH
The Albert Einstein College of Medicine, Department of Biochemistry, 1300 Morris Park Ave., Bronx, New York 10461, USA.
Nandy
Sandip K
SK
Lawrence
David S
DS
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
D004791:Enzyme Inhibitors; D010455:Peptides; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha