<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Fichna,J.</style></author><author><style face="normal" font="default" size="100%">do-Rego,J.C.</style></author><author><style face="normal" font="default" size="100%">Janecki,T.</style></author><author><style face="normal" font="default" size="100%">Staniszewska,R.</style></author><author><style face="normal" font="default" size="100%">J Poels</style></author><author><style face="normal" font="default" size="100%">J. Vanden Broeck</style></author><author><style face="normal" font="default" size="100%">Costentin,J.</style></author><author><style face="normal" font="default" size="100%">Schiller,P.W.</style></author><author><style face="normal" font="default" size="100%">A.E. Janecka</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Novel highly potent mu-opioid receptor antagonist based on endomorphin-2 structure4392</style></title><secondary-title><style face="normal" font="default" size="100%">Bioorg.Med.Chem.Lett.</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">0</style></keyword><keyword><style  face="normal" font="default" size="100%">a</style></keyword><keyword><style  face="normal" font="default" size="100%">Activity</style></keyword><keyword><style  face="normal" font="default" size="100%">Aequorin</style></keyword><keyword><style  face="normal" font="default" size="100%">agonists</style></keyword><keyword><style  face="normal" font="default" size="100%">an</style></keyword><keyword><style  face="normal" font="default" size="100%">Analgesics</style></keyword><keyword><style  face="normal" font="default" size="100%">Analgesics,Opioid</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">antagonists &amp; inhibitors</style></keyword><keyword><style  face="normal" font="default" size="100%">article</style></keyword><keyword><style  face="normal" font="default" size="100%">AS</style></keyword><keyword><style  face="normal" font="default" size="100%">Calcium</style></keyword><keyword><style  face="normal" font="default" size="100%">chemical synthesis</style></keyword><keyword><style  face="normal" font="default" size="100%">chemistry</style></keyword><keyword><style  face="normal" font="default" size="100%">Cho Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Chromatography,High Pressure Liquid</style></keyword><keyword><style  face="normal" font="default" size="100%">Cricetinae</style></keyword><keyword><style  face="normal" font="default" size="100%">Cricetulus</style></keyword><keyword><style  face="normal" font="default" size="100%">Drug Design</style></keyword><keyword><style  face="normal" font="default" size="100%">drug effects</style></keyword><keyword><style  face="normal" font="default" size="100%">electronic</style></keyword><keyword><style  face="normal" font="default" size="100%">EVALUATION</style></keyword><keyword><style  face="normal" font="default" size="100%">im</style></keyword><keyword><style  face="normal" font="default" size="100%">improve</style></keyword><keyword><style  face="normal" font="default" size="100%">in vivo</style></keyword><keyword><style  face="normal" font="default" size="100%">Institute</style></keyword><keyword><style  face="normal" font="default" size="100%">IS</style></keyword><keyword><style  face="normal" font="default" size="100%">IT</style></keyword><keyword><style  face="normal" font="default" size="100%">journal</style></keyword><keyword><style  face="normal" font="default" size="100%">Laboratories</style></keyword><keyword><style  face="normal" font="default" size="100%">Less</style></keyword><keyword><style  face="normal" font="default" size="100%">medical</style></keyword><keyword><style  face="normal" font="default" size="100%">metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Oligopeptides</style></keyword><keyword><style  face="normal" font="default" size="100%">ON</style></keyword><keyword><style  face="normal" font="default" size="100%">Pain Measurement</style></keyword><keyword><style  face="normal" font="default" size="100%">pharmacology</style></keyword><keyword><style  face="normal" font="default" size="100%">profile</style></keyword><keyword><style  face="normal" font="default" size="100%">Protein Conformation</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptor</style></keyword><keyword><style  face="normal" font="default" size="100%">receptors</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptors,Opioid,mu</style></keyword><keyword><style  face="normal" font="default" size="100%">report</style></keyword><keyword><style  face="normal" font="default" size="100%">Research</style></keyword><keyword><style  face="normal" font="default" size="100%">Research Support</style></keyword><keyword><style  face="normal" font="default" size="100%">SB - IM</style></keyword><keyword><style  face="normal" font="default" size="100%">Spectrometry,Mass,Fast Atom Bombardment</style></keyword><keyword><style  face="normal" font="default" size="100%">structure</style></keyword><keyword><style  face="normal" font="default" size="100%">Test</style></keyword><keyword><style  face="normal" font="default" size="100%">Universities</style></keyword><keyword><style  face="normal" font="default" size="100%">university</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2008</style></year><pub-dates><date><style  face="normal" font="default" size="100%">15/2/2008</style></date></pub-dates></dates><number><style face="normal" font="default" size="100%">1353</style></number><volume><style face="normal" font="default" size="100%">18</style></volume><pages><style face="normal" font="default" size="100%">1350 - 1353</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">The mu-opioid agonists endomorphin-1 (Tyr-Pro-Trp-Phe-NH(2)) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH(2)) exhibit an extremely high selectivity for the mu-opioid receptor and thus represent a potential framework for modification into mu-antagonists. Here we report on the synthesis and biological evaluation of novel [d-2-Nal(4)]endomorphin-2 analogs, [Sar(2),d-2-Nal(4)]endomorphin-2 and [Dmt(1),Sar(2),d-2-Nal(4)]endomorphin-2 (Dmt=2'6'-dimethyltyrosine; Sar=N-methylglycine, sarcosine; d-2-Nal=3-(2-naphthyl)-d-alanine). [Dmt(1),Sar(2),d-2-Nal(4)]endomorphin-2 possessed very high affinity for the mu-opioid receptor (IC(50)=0.01+/-0.001 nM) and turned out to be a potent and extremely selective mu-opioid receptor antagonist, as judged by the in vitro aequorin luminescence-based calcium assay (pA(2)=9.19). However, in the in vivo hot plate test in mice this analog was less potent than our earlier mu-opioid receptor antagonist, [Dmt(1),d-2-Nal(4)]endomorphin-2 (antanal-2). The exceptional mu-opioid receptor in vitro activity and selectivity of [Dmt(1), Sar(2),d-2-Nal(4)]endomorphin-2 makes this analog a valuable pharmacological tool, but further modifications are needed to improve its in vivo profile</style></abstract><issue><style face="normal" font="default" size="100%">4</style></issue><custom1><style face="normal" font="default" size="100%">4392</style></custom1><section><style face="normal" font="default" size="100%">1350</style></section></record></records></xml>