P11

P11 is a useful building block in the synthesis of various pharmaceuticals

This potent PDZ motif-containing anti-angiogenic agent (FW = 720.78 g/mol; CAS 848644-86-0; Sequence: HSDVHK-NH2) targets the integrin αvβ3-vitronectin interaction, blocking proliferation and inducing apoptosis in human vascular endothelial cells (HUVECs). Arg-Gly-Asp (or RGD) binding-site recognition by P11 is site-specific, showing a strong antagonism against αvβ3-vitronectin interaction, IC50 = 26 nM. The binding orientation of docked P11 in αvβ3 is similar to that for RGD, suggesting a divalent metal-ion coordination is a common driving force for the formation of both SDV·αvβ3 and RGD·αvβ3 complexes. P11 appears to inhibit b-Fibroblast Growth Factor (or bFGF) -induced HUVEC proliferation via mitogen-activated protein kinase kinase and extracellular- signal regulated kinase inhibition as well as p53-mediated apoptosis related with activation of caspases. (Note: Consisting of 80-90 amino-acids in far-flung signaling proteins and binding to short C-terminal regions in protein interaction partners, “PDZ” is an acronym that includes the first letters of Post-synaptic density protein (PSD95), Drosophila Dlg1 tumor suppressor, and Zonula occludens-1 protein (zo-1), the first proteins discovered to share this domain.)