Download MendeleyThe reversed binding of beta-phenethylamine inhibitors of DPP-IV: X-ray structures and properties of novel fragment and elaborated inhibitors.
Nordhoff, S., Cerezo-Galvez, S., Feurer, A., Hill, O., Matassa, V.G., Metz, G., Rummey, C., Thiemann, M., Edwards, P.J.(2006) Bioorg Med Chem Lett 16: 1744-1748
- PubMed: 16376544
- DOI: https://doi.org/10.1016/j.bmcl.2005.11.103
- Primary Citation of Related Structures:
2BUA, 2BUB, 2BUC - PubMed 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.
Organizational Affiliation:
Medicinal Chemistry, Santhera Pharmaceuticals, Im Neuenheimer Feld 518-519, D-69120 Heidelberg, Germany. sonja.nordhoff@santhera.com
