Sub-nanomolar hMC1R agonists by end-capping of the melanocortin tetrapeptide His-D-Phe-Arg-Trp-NH2
Sub-nanomolar hMC1R agonists by end-capping of the melanocortin tetrapeptide His-D-Phe-Arg-Trp-NH2
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DOI：
10.1016/s0960-894x(03)00552-3
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发表时间：
2003-08-18
影响因子：
2.7
通讯作者：
Knittel, JJ
中科院分区：
文献类型：
--
作者：
Koikov, LN;Ebetino, FH;Knittel, JJ
合成了23个用羧酸和磺酸封端的核心片段His（6）-D-Phe（7）-Arg（8）-Trp（9）-NH 2的衍生物，并在人黑皮质素受体（hMC 1、hMC 3和hMC 4 R）上进行了评价。该系列中的SAR使我们能够定位His（6）结合位点附近的hMCR，并设计出一种超级有效的MC 1 R激动剂LK-184，Ph（CH 2）（3）CO-HiS-D-Phe-Arg-Trp-NH 2（19），EC 50为0.01 nM（MC 3和MC 4 Rs为5 nM）。(C)2003爱思唯尔有限公司。保留所有权利。
Twenty three derivatives of the core fragment His(6)-D-Phe(7)-Arg(8)-Trp(9)-NH2 end-capped with carboxylic and sulfonic acids were synthesized and evaluated at human melanocortin receptors (hMC1, hMC3, and hMC4Rs). The SAR within this series allowed us to map the hMCRs near the His(6) binding site and design a superpotent MC1R agonist, LK-184, Ph(CH2)(3)CO-HiS-D-Phe-Arg-Trp-NH2 (19) with EC50 0.01 nM (5 nM at MC3 and MC4Rs). (C) 2003 Elsevier Ltd. All rights reserved.