The reversed binding of beta-phenethylamine inhibitors of DPP-IV: X-ray structures and properties of novel fragment and elaborated inhibitors |
| |
Authors: | Nordhoff Sonja Cerezo-Gálvez Silvia Feurer Achim Hill Oliver Matassa Victor G Metz Günther Rummey Christian Thiemann Meinolf Edwards Paul J |
| |
Institution: | Medicinal Chemistry, Santhera Pharmaceuticals, Im Neuenheimer Feld 518-519, D-69120 Heidelberg, Germany. sonja.nordhoff@santhera.com |
| |
Abstract: | The co-crystal structure of beta-phenethylamine fragment inhibitor 5 bound to DPP-IV revealed that the phenyl ring occupied the proline pocket of the enzyme. This finding provided the basis for a general hypothesis of a reverse binding mode for beta-phenethylamine-based DPP-IV inhibitors. Novel inhibitor design concepts that obviate substrate-like structure-activity relationships (SAR) were thereby enabled, and novel, potent inhibitors were discovered. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |