Synthetic studies on enkephalin analogs. III. A highly potent enkephalin analog, H-Tyr-D-Met(O)-Gly-Phe-NHNH-CO-CH2CH3.
- 1 January 1981
- journal article
- research article
- Published by Pharmaceutical Society of Japan in CHEMICAL & PHARMACEUTICAL BULLETIN
- Vol. 29 (12) , 3646-3659
- https://doi.org/10.1248/cpb.29.3646
Abstract
Tetrapeptide acyl-hydrazide analogs [35] of enkephalin substituted at position 2 were synthesized. Substitution of D-Ala at position 2 of H-Tyr-D-Ala-Gly-Phe-NHNH-CO-R (R = lower alkyl), by D-Met (O), D-Gln, D-Glu(NH-CH3) or D-Thr enhanced the analgesic potency, but substitution by D-Glu or Ser resulted in an analog with no antinociceptive activity. Among the analogs synthesized, the D-Met(O)-analog was the most potent and H-Tyr-D-Met(O)-Gly-Phe-NHNH-CO-CH2CH3 exhibited analgesic activity 4 times more potent than that of morphine in mice following s.c. injection. Structure-activity relations for position 2 of the enkephalin-like tetrapeptide are discussed.This publication has 9 references indexed in Scilit:
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