Nair Padma, Yamamoto Takashi, Cowell Scott, Kulkarni Vinod, Moye Sharif, Navratilova Edita, Davis Peg, Ma Shou-Wu, Vanderah Todd W, Lai Josephine, Porreca Frank, Hruby Victor J
Department of Chemistry and Biochemistry, University of Arizona, 1306 East University Boulevard, Tucson, AZ 85721, USA.
Department of Pharmacology, University of Arizona, 1501 North Campbell Avenue, Tucson, AZ 85724, USA.
Bioorg Med Chem Lett. 2015 Sep 1;25(17):3716-20. doi: 10.1016/j.bmcl.2015.06.030. Epub 2015 Jun 15.
Several bifunctional peptides were synthesized and characterized based on the pentapeptide-derived ligand NP30 (1: Tyr-DAla-Gly-Phe-Gly-Trp-O-[3',5'-Bzl(CF3)2]). Modification and truncation of amino acid residues were performed, and the tripeptide-derived ligand NP66 (11: Dmt-DAla-Trp-NH-[3',5'-(CF3)2-Bzl]) was obtained based on the overlapping pharmacophore concept. The Trp(3) residue of ligand 11 works as a message residue for both opioid and NK1 activities. The significance lies in the observation that the approach of appropriate truncation of peptide sequence could lead to a tripeptide-derived chimeric ligand with effective binding and functional activities for both mu and delta opioid and NK1 receptors with agonist activities at mu and delta opioid and antagonist activity at NK1 receptors, respectively.
基于五肽衍生配体NP30（1：Tyr-DAla-Gly-Phe-Gly-Trp-O-[3',5'-Bzl(CF3)2]）合成并表征了几种双功能肽。对氨基酸残基进行了修饰和截短，并基于重叠药效团概念获得了三肽衍生配体NP66（11：Dmt-DAla-Trp-NH-[3',5'-(CF3)2-Bzl]）。配体11的Trp(3)残基作为阿片样物质和NK1活性的信息残基。其意义在于观察到适当截短肽序列的方法可导致一种三肽衍生的嵌合配体，该配体对μ和δ阿片样物质受体以及NK1受体具有有效的结合和功能活性，分别对μ和δ阿片样物质受体具有激动剂活性，对NK1受体具有拮抗剂活性。
