Metabolic Stability of Peptidomimetics:
Source: Chemical Biology & Drug Design, Volume 78, Number 5, 1 November 2011 , pp. 887-892(6)
Abstract:Linear peptides suffer from poor pharmacokinetic and pharmacodynamic properties. Peptidomimetics are designed to overcome these pharmacological drawbacks while maintaining the biological effects of the parent peptides. Aza‐peptides, in which an alpha carbon is replaced with nitrogen, are promising peptidomimetic analogs; however, little is known about the stability of these analogs toward enzymatic degradation. We performed systematic aza and N‐methyl scans of a PKB/Akt inhibitor, PTR6154. We evaluated the stability of the aza‐scan and N‐methyl scan libraries toward enzymatic degradation by trypsin/chymotrypsin. Our results indicate that the modification site is important for metabolic stability and that aza‐peptides have a more global effect than N‐methylation, affecting cleavage sites distant from the modification site.
Document Type: Research Article
Affiliations: 1: Institute of Chemistry, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel 2: Unit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel
Publication date: 2011-11-01