The relaxin peptide family--structure, function and clinical applications.
The relaxin peptide family--structure, function and clinical applications.
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DOI：
10.2174/092986611794578396
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发表时间：
2011-02
影响因子：
1.6
通讯作者：
Linda J. Chan;M. Hossain;C. Samuel;F. Separovic;J. Wade
中科院分区：
文献类型：
--
作者：
Linda J. Chan;M. Hossain;C. Samuel;F. Separovic;J. Wade
人类松弛素肽家族包括7个成员，松弛素-1、-2和-3以及胰岛素样肽3、4、5和6。它是胰岛素超级家族的一个分支。每个成员由两条链组成，通常被称为A和B，它们由两个链间二硫键和A链内的另一个链内二硫键连接在一起。存在于每条链中的半胱氨酸残基，以及独特的二硫键模式，在超家族的所有成员中都是保守的。这些复杂肽的化学合成提出了一个重大的挑战。在过去，两条合成的s -还原链在氧化条件下随机结合，形成三个二硫键。如今，在高效固相肽合成方法的帮助下，结合选择性s -巯基保护基团，通过三个二硫键的顺序化学形成单个A链和B链的组合现在可能导致这些肽的良好产量。松弛素家族成员与g蛋白偶联受体（gpcr）结合，被归类为松弛素家族肽（RXFP）受体。本文概述了各种独特的受体-配体相互作用，以及松弛素肽家族成员的生理作用，最后介绍了它们过去和现在的临床应用。
The relaxin peptide family in humans consists of seven members, relaxin-1, -2 and -3 and insulin-like (INSL) peptides 3, 4, 5 and 6. It is an offshoot of the large insulin superfamily. Each member consists of two chains, commonly referred to as A and B, which are held together by two inter-chain disulfide bonds and another intra-chain disulfide bond present within the A chain. The cysteine residues present in each chain, together with the distinctive disulfide bonding pattern, are conserved across all members of the superfamily. The chemical synthesis of these complex peptides poses a significant challenge. In the past, random combination of the two synthetic S-reduced chains under oxidizing conditions was utilized to form the three disulfide bonds. Nowadays, with the aid of highly efficient solid phase peptide synthesis methodologies, in conjunction with selective S-thiol-protecting groups, combination of individual A- and B- chains by sequential chemical formation of each of the three disulfide bonds is now possible resulting in good yields of these peptides. The relaxin peptide family members bind to G-protein coupled receptors (GPCRs) which have been classified as relaxin family peptide (RXFP) receptors. The various unique receptor-ligand interactions are outlined in this review, together with the physiological roles of the relaxin peptide family members and lastly their past and present clinical applications.