Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1379104 | Bioorganic & Medicinal Chemistry Letters | 2006 | 5 Pages |
The co-crystal structure of β-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 β-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.
Graphical abstractThe co-crystal structure of β-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 β-phenethylamine-based DPP-IV inhibitors, allowing novel inhibitor design concepts that obviate substrate-like structure–activity relationships (SAR).Figure optionsDownload full-size imageDownload as PowerPoint slide