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Stepwise Combinatorial Evolution of Akt Bisubstrate Inhibitors
Author(s) -
Lee Jung Hwan,
Kumar Sanjai,
Lawrence David S.
Publication year - 2008
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200700583
Subject(s) - computational biology , protein kinase b , directed evolution , peptide , computer science , chemistry , kinase , combinatorial chemistry , phosphorylation , biochemistry , biology , gene , mutant
Bisubstrate analogue inhibitors have recently received considerable attention as mechanistic and structural probes of protein kinases. A stepwise library‐based strategy was employed to create a potent bisubstrate inhibitor of Akt from an extraordinarily weak nonphosphorylatable peptide. The combinatorial methodology offers a means to retain desirable properties during the directed evolution of inhibitory species.