Design,Systhesis And Analgesia Activity Of Edomorphin-1 Analogs With Multi-locus Modification

In 1997,Zadina,a nurobiologist in America Touraine university,and his colleges got a strong ligand binding MOR,which have highly selective and affinity.They got it from ox brain by means of immunohistochemisty.This ligand was called endogenous opioid peptides and its structure has twe kinds of ligands,which were called endomorphin-1(EM-1,Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (EM-1,Tyr-Pro-Phe-Phe-NH2)However,in several study,EM-2 have poor characteristics in therapeutics and have lower analgesia than EM-1,and also have higher side effect than EM-1.In unorganized enzymolysis experiment,EM-1 have higher stability than EM-2o So In this paper, our study is to aim directly at EM-1.endomorohin is in the irreplaceable position to treat severe pain.To be worth to say,endoporphin have distinguished treatment effectiveness in the Nerve Pain. At the same time, in a lower drug level, endoporphin have little side effect.But it is not good that opioid drugs can not be applied clinically, opioid drugs also generate many side effect including constipation, addiction,tolerance, vomiting and Respiratory Depression etc.The other reasons which lead to not applying in clinic are the short analgesia time,low stability in enzymolysis and low abilty to penetrate BBB.In this paper,we substitute L-Pro-Trp with L-Pro, D-Pro, D-Ala-Gly,respectively.And modifing N terminal with guanidinium group, C terminal with amination group.and then we get five endomorphin-1 anologes,they are named GLPF, GDPF, HLP, HDP, GAGPNH2.We did several experiments to check their physical activity, including analgesia time,the stability in enzymolysis and affinity.The results are as follows:tripeptide 1,2,3 and 4 which every activity are relativly low,but anologe 5(GU-Tyr-Ala-Gly-Phe-(4-NH2)) have high activity.