Enkephalin pseudopeptides: resistance to in vitro proteolytic degradation afforded by amide bond replacements extends to remote sites |
| |
Authors: | D E Benovitz A F Spatola |
| |
Institution: | Department of Chemistry, University of Louisville, Louisville, KY 40292 USA |
| |
Abstract: | Five analogs of leucine enkephalin containing the CH2S group as an amide bond replacement were evaluated with respect to resistance toward degradation by human serum in an HPLC-based assay using both ultraviolet and electrochemical detection. Analogs with the modification at the 1-2, 2-3, 3-4, or 4-5 peptide linkages demonstrated half-lives of 118, 85, 134, and 318 min vs. 12 min for the parent peptide. A pseudopeptide analog with additional D-Ala2 protection had a half-life of greater than 1000 min, while the potent D-Ala2]-leucine enkephalin analog showed approximately a 10-fold increase in stability. The significant increase in stability for a compound with protection only at the C-terminus suggests that serum enzymes may have greater specificity toward backbone changes than previously realized. |
| |
Keywords: | Leucine enkephalin Backbone modification HPLC-EC HPLC assay system Serum degradation EC detection Pseudopeptides Amide bond replacement |
本文献已被 ScienceDirect 等数据库收录! |
|