Development of mu-opioid receptor ligands by using unique L-tyrosine analogues

摘要

Opioid studies revealed that the replacement of the N-terminal tyrosine in opioid peptides with 2',6'-dimethyl-L-tyrosine(Dmt)enhanced both opioid receptor binding affinity and functional bioactivity.In order to develop potent opioid ligands,it seemed prudent therefore to study the structure-activity relationship of the alkyl groups on the aromatic ring of the Tyr residue.In this study,six L-Tyr analogues containing different alkyl groups [2'-monomethyl-tyrosine(Mmt),2' -ethyl-6 -methyl-tyrosine(Emt),2' -isopropyl-6'-methyl-tyrosine(Imt),2',6'-diethyl-tyrosine(Det),2',6'-diisopropyl-tyrosine(Dit)and 2',3',6' -trimethyl-tyrosine(Tmt)],were developed and their bioactivities were evaluated by incorporation into endomorphin-2(EM-2:YPFF-NH_2).