Further structure-activity studies of lactam derivatives of MT-H and SHU-9119: Their activity and selectivity at human melanocortin receptors 3, 4, and 5
Further structure-activity studies of lactam derivatives of MT-H and SHU-9119: Their activity and selectivity at human melanocortin receptors 3, 4, and 5
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DOI：
10.1016/j.peptides.2007.02.012
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发表时间：
2007-06-01
期刊：
影响因子：
3
通讯作者：
Hruby, Victor J.
中科院分区：
文献类型：
--
作者：
Grieco, Paolo;Cai, Minying;Hruby, Victor J.
Recently we have demonstrated that replacing His(6) by constrained amino acids(2) in the well-known antagonist SHU-9119 resulted in potent and selective antagonist ligands especially at the hMC3R and hMC5 receptors. With the aim to further explore position 6 in the sequence of SHU-9119 and MT-II, we have designed, synthesized, and pharmacologically characterized a series of peptide analogues of MT-II and SHU-9119 at the human melanocortin receptors subtypes MC3R, MC4R and MC5R.所有这些肽均在6位上用可商购的限制性氨基酸进行修饰。在这项研究中，我们鉴定了 hMC4R 的新选择性配体和 hMC3/hMC4 受体的拮抗剂。 Additionally, we have discovered an interesting new selective antagonist at the hMC3R, Ac-Nle-c[Asp-beta Ala-DNal(2')-Arg-Trp-Lys]-NH2 (2, PG-106) which represents an important tool in further biological investigations of the hMC3R. PG-106 将有助于进一步区分负责 hMC3R、hMC4R 和 hMC5R 选择性的子结构特征。 (c) 2007 Elsevier Inc. 保留所有权利。
Recently we have demonstrated that replacing His(6) by constrained amino acids(2) in the well-known antagonist SHU-9119 resulted in potent and selective antagonist ligands especially at the hMC3R and hMC5 receptors. With the aim to further explore position 6 in the sequence of SHU-9119 and MT-II, we have designed, synthesized, and pharmacologically characterized a series of peptide analogues of MT-II and SHU-9119 at the human melanocortin receptors subtypes MC3R, MC4R and MC5R. All these peptides were modified at position 6 with constrained amino acids which are commercially available. In this study, we have identified new selective ligands for the hMC4R, and an antagonist for the hMC3/hMC4 receptors. Additionally, we have discovered an interesting new selective antagonist at the hMC3R, Ac-Nle-c[Asp-beta Ala-DNal(2')-Arg-Trp-Lys]-NH2 (2, PG-106) which represents an important tool in further biological investigations of the hMC3R. PG-106 will be useful in further efforts to differentiate the substructural features responsible for selectivity at the hMC3R, hMC4R, and hMC5R. (c) 2007 Elsevier Inc. All rights reserved.