Discovery of thioazepinone ligands for Src SH2: from non-specific to specific binding.
The structure-based design and synthesis of new thioazepinones as ligands for Src SH2 protein is presented. From benzothioazepinones, ligands with somewhat unspecific binding properties, simpler thioazepinones were designed, the best ones demonstrated nanomolar affinity for Src SH2. A few of these new ligands were crystallized with the protein and demonstrated a specific binding mode with the protein.
Lesuisse
D
D
Department of Medicinal Chemistry, Aventis, 102 route de Noisy, 93235 Romainville Cedex, France. dominique.lesuisse@aventis.com
Deprez
P
P
Albert
E
E
Duc
T T
TT
Sortais
B
B
Gofflo
D
D
Jean-Baptiste
V
V
Marquette
J
J
Schoot
B
B
Sarubbi
E
E
Lange
G
G
Broto
P
P
Mandine
E
E
D001381:Azepines / Q000494:pharmacology*; D001665:Binding Sites; D008024:Ligands; D008958:Models, Molecular; D015688:Oncogene Protein pp60(v-src) / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D018909:src Homology Domains
D001381:Azepines; D008024:Ligands; D015688:Oncogene Protein pp60(v-src)