Dermorphin analogs: resistance to in vitro enzymatic degradation is not always increased by additional D-amino acid substitutions.
Dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) and seven analogs were examined for their biostability towards rat brain homogenate; half-lives for the parent were 127 min and 48 min, respectively, with Gly4-Tyr5 cleavage confirmed by collection and identification of the N-terminal fragment. Surprisingly, several analogs with additional D-amino acid substitutions were cleaved more rapidly than the parent, suggesting the importance of remote secondary structural features for differential enzyme susceptibility.
D000701:Analgesics, Opioid / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004386:Duodenum / Q000378:metabolism; D006207:Half-Life; D008297:Male; D009842:Oligopeptides / Q000378:metabolism*; D018847:Opioid Peptides; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000701:Analgesics, Opioid; D009842:Oligopeptides; D018847:Opioid Peptides; C030058:dermorphin