Methionine oxidation enhances opioid activity of an enkephalin analog.
D-ala2-met-sulfoxide5-enkephalinamide, DALA(0), was synthesized by oxidizing the 5-methionine residue of D-ala2-met5-enkephalinamide (DALA). Antinociception was assessed on the hot-plate and catalepsy estimated using an immobility test in rats administered DALA, DALA(0) and morphine intraventricularly. By comparing areas under time-effect curves, DALA(0) was 30 times more antinociceptive and up to 40 times more cataleptogenic than DALA. For comparison, morphine induced one-tenth the antinociception and one-fortieth the immobility caused by DALA(0). These results demonstrate that the opiate activity of DALA is clearly enhanced by oxidation of its terminal methionine.
D000701:Analgesics, Opioid / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008297:Male; D008715:Methionine; D008845:Microinjections; D009020:Morphine / Q000494:pharmacology; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000701:Analgesics, Opioid; D004744:Enkephalin, Methionine; C022118:enkephalinamide-Met, Ala(2)-; C037423:enkephalinamide-Met sulfoxide, Ala(2)-; D009020:Morphine; D008715:Methionine