Resistance of FK 33-824 and other enkephalin analogues to peptidase degradation.
The stability of analogues of Met-enkephalin containing different chemical substitutions in the amino acid sequence to enzymatic degradation by a mouse brain extract and by rat striatal membranes have been compared. On incubation with the mouse brain extract, the naturally occurring Met-enkephalin was completely destroyed within 5 min and 50% of (D-Ala2)Met-enkephalinamide was degraded within 2 1/2 hr, with the release of Tyr, Phe, Met, D-Ala-Gly and partially (D-)Ala and Gly. (D-Ala2, MePhe4, Met(O)ol5) enkephalin (FK 33-824) was degraded to 50% within 5 hr, giving merely Tyr and the tetrapeptide D-Ala-Gly-MePhe-Met(O)ol as degradation products. No metabolism was observed after incubation for 24 hr of (MeTyr1, D-Ala2, MePhe4, Met(O)ol5) enkephalin (FW 34-569) with the mouse brain extract. On incubation with rat striatal membranes in the presence of puromycin, Met-enkephalin was rapidly inactivated, principally by cleavage of the Gly3-Phe4 bond, whereas FK 33-824 was not split.
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology*; D003342:Corpus Striatum / Q000201:enzymology; D004723:Endorphins / Q000378:metabolism*; D004745:Enkephalins / Q000378:metabolism*; D051379:Mice; D010446:Peptide Fragments; D010447:Peptide Hydrolases / Q000494:pharmacology*; D014020:Tissue Extracts / Q000494:pharmacology*
D004723:Endorphins; D004745:Enkephalins; D010446:Peptide Fragments; D014020:Tissue Extracts; D010447:Peptide Hydrolases