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.
Sperl
Bianca
B
Department of Molecular Biology, Max Planck Institute of Biochemistry, and Center for Integrated Protein Science Munich, Am Klopferspitz 18, 82152 Martinsried, Germany.
Seifert
Markus H J
MH
Berg
Thorsten
T
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