[D-Met2,Pro5] enkephalin [N1.5-beta-D-glucopyranosyl] amide: a glycosylpeptide with high antinociceptive activity.
Different synthetic strategies have been attempted for the synthesis of a glycosylpeptide resulting from the covalent bonding of a sugar residue to the C-terminal carboxyl group of an enkephalin related pentapeptide. The final structure is: Tyr-D-Met-Gly-Phe-Pro [N1.5-beta-D-glucopyranosyl] amide. The in vitro potency on the GPI test of this analogue was IC50 = 64.0 nM. However, its antinociceptive activity by tail immersion tests, after intraperitoneal administration, was 2000 and 200 times higher than morphine in rats and mice, respectively.
Torres
J L
JL
Biological Organic Chemistry Department, Faculty of Medicine, University of Salamanca, Spain.
Reig
F
F
Valencia
G
G
Rodríguez
R E
RE
García-Antón
J M
JM
D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004745:Enkephalins; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000700:Analgesics; D004745:Enkephalins; D007202:Indicators and Reagents; C056982:enkephalin, Met(2)-ProNH2(5)(N(1.5)-glucopyranosyl); D004744:Enkephalin, Methionine; D009020:Morphine