Lovett J A, Portoghese P S
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis 55455.
NIDA Res Monogr. 1986;75:185-8.
N,N-Dialkylated leucine enkephalin analogs containing melphalan in place of Phe4 were synthesized as potentially irreversible antagonists of the delta opioid receptor. These compounds, along with the corresponding Phe4 peptides, were tested for both agonist and antagonist activity in the GPI and MVD smooth muscle preparations. All but one of the compounds showed antagonist activity at 10(-6) M against [D-Ala2,D-Leu5] enkephalin in the MVD when tested under reversible conditions; in all cases the Mel4 peptide had lower activity against DADLE than did the corresponding Phe4 peptide. At high concentrations (10(-5) M) the active Mel4 analogs, (benzyl)2Tyr-Gly-Gly-Mel-Leu and (allyl)2Tyr-Aib-Aib-Mel-Leu, both showed weak irreversible antagonism at the delta receptor.
合成了用美法仑取代苯丙氨酸4的N，N-二烷基化亮氨酸脑啡肽类似物，作为δ阿片受体的潜在不可逆拮抗剂。这些化合物以及相应的苯丙氨酸4肽，在GPI和MVD平滑肌制剂中测试了激动剂和拮抗剂活性。在可逆条件下测试时，除一种化合物外，所有化合物在10（-6）M时对MVD中的[D-Ala2，D-Leu5]脑啡肽均表现出拮抗剂活性；在所有情况下，Mel4肽对DADLE的活性均低于相应的Phe4肽。在高浓度（10（-5）M）下，活性Mel4类似物（苄基）2Tyr-Gly-Gly-Mel-Leu和（烯丙基）2Tyr-Aib-Aib-Mel-Leu在δ受体上均表现出弱的不可逆拮抗作用。
