Glycoconjugates of opioid peptides. Synthesis and biological activity of [Leu5]enkephalin related glycoconjugates with amide type of linkage.
Three N-glycoconjugates of the general formula H-Tyr-Gly-Gly-Phe-Leu-NH-R (R = carbohydrate residue) were synthesized in order to determine the influence of some carbohydrate molecules (6-amino-6-deoxy-D-glucopyranose, 2-amino-2-deoxy-D-glucopyranose, beta-D-glucopyranosylamine) on the biological activity, conformation, and stability of the opioid pentapeptide [Leu5]enkephalin. For the preparation of this compound different methods of peptide synthesis (active ester and mixed anhydride) were investigated. In comparison with [Leu5]enkephalin, all three N-glycoconjugates showed higher potency in the guinea pig ileum assay and lower potency in the mouse vas deferens assay, indicating a decrease in delta opioid receptor selectivity.
Varga-Defterdarović
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L
Ruder Bosković Institute, Department of Organic Chemistry and Biochemistry, Zagreb, Yugoslavia.
Horvat
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S
Chung
N N
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Schiller
P W
PW
D000595:Amino Acid Sequence; D000818:Animals; D004743:Enkephalin, Leucine / Q000737:chemistry* / Q000494:pharmacology; D005944:Glucosamine / Q000031:analogs & derivatives / Q000737:chemistry; D006001:Glycoconjugates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D014649:Vas Deferens / Q000187:drug effects
D006001:Glycoconjugates; C075821:6-amino-6-deoxyglucopyranose; D004743:Enkephalin, Leucine; C075822:glucopyranosylamine; D005944:Glucosamine