Natural product inhibitors of protein-protein interactions mediated by Src-family SH2 domains.
In this Letter, we report the natural products salvianolic acid A, salvianolic acid B, and caftaric acid as inhibitors of the protein-protein interactions mediated by the SH2 domains of the Src-family kinases Src and Lck, two established disease targets. Moreover, we propose a binding mode for the inhibitors based on molecular modeling, which will facilitate chemical optimization efforts of these important lead structures for drug discovery.
Department of Molecular Biology, Max Planck Institute of Biochemistry, and Center for Integrated Protein Science Munich, Am Klopferspitz 18, 82152 Martinsried, Germany.
Bianca
B
Sperl
Markus H J
MH
Seifert
Thorsten
T
Berg
D001572:Benzofurans / Q000494:pharmacology; D001688:Biological Products / Q000494:pharmacology*; D002109:Caffeic Acids / Q000494:pharmacology; D055808:Drug Discovery; D006801:Humans; D007773:Lactates / Q000494:pharmacology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors; D008958:Models, Molecular; D010636:Phenols / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000037:antagonists & inhibitors; D018909:src Homology Domains / Q000187:drug effects*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*; D053630:Depsides
D001572:Benzofurans; D001688:Biological Products; D002109:Caffeic Acids; D007773:Lactates; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D010636:Phenols; D047428:Protein Kinase Inhibitors; D016392:Proto-Oncogene Proteins pp60(c-src); D019061:src-Family Kinases; C066201:salvianolic acid A; C076944:salvianolic acid B; D053630:Depsides; C515101:caftaric acid