[Effect of structural changes of Pro6 in dermorphin molecule on its antinociceptive activity].
We studied effect of dermorphin (H-Tyr-DAla-Phe-Gly-Tyr-Pro-Ser-NH2) and its analogs with modified amino acid residue proline in position 6, H-Tyr-DAla-Phe-Gly-Tyr-[DPro]-Ser-NH2, H-Tyr-DAla-Phe-Gly-Tyr-[dehydro-Pro]-Ser-NH2, and H-Tyr-DAla-Phe-Gly-Tyr-[D-dehydro-Pro]-Ser-NH2, on nociception in the tail-flick and hot plate tests after intraperitoneal injection. Replacement of LPro with the stereoisomer DPro as well as Pro dehydration (LdHPro) was shown to increase antinociceptive activity. Replacement of LdHPro with DdHPro cancelled the activity in the tail-flick test. All three dermorphin analogs retained antinociceptive activity in the hot plate test; however, the effect of dermorphin was more pronounced.
Semenov Institute of Chemical Physics, Russian Academy of Sciences, ul. Kosygina 4, Moscow, 117991 Russia.
L S
LS
Guzevatykh
T G
TG
Emel'ianova
A B
AB
Usenko
L A
LA
Andreeva
L Iu
LIu
Alfeeva
T A
TA
Voronina
N F
NF
Miasoedov
D000700:Analgesics / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D021461:Animals, Outbred Strains; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008297:Male; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D018847:Opioid Peptides; D011392:Proline / Q000737:chemistry; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D013329:Structure-Activity Relationship
D000700:Analgesics; D009842:Oligopeptides; D018847:Opioid Peptides; C030058:dermorphin; D011392:Proline