title: Enkephalin pseudopeptides: resistance to in vitro proteolytic degradation afforded by amide bond replacements extends to remote sites.
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.
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000097:blood*; D006801:Humans; D007700:Kinetics; D013329:Structure-Activity Relationship; D009626:Terminology as Topic
chemical_list: D004743:Enkephalin, Leucine