Article ID Journal Published Year Pages File Type
1379104 Bioorganic & Medicinal Chemistry Letters 2006 5 Pages PDF
Abstract

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

Related Topics
Physical Sciences and Engineering Chemistry Organic Chemistry
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