Natural Proline-Rich Cyclopolypeptides from Marine Organisms: Chemistry, Synthetic Methodologies and Biological Status.
Natural Proline-Rich Cyclopolypeptides from Marine Organisms: Chemistry, Synthetic Methodologies and Biological Status.
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DOI：
10.3390/md14110194
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发表时间：
2016-10-26
期刊：
影响因子：
5.4
通讯作者：
Maharaj S
中科院分区：
文献类型：
--
作者：
Fang WY;Dahiya R;Qin HL;Mourya R;Maharaj S
近年来，肽作为治疗剂获得了越来越多的关注。超过60种肽类药物已进入市场，造福于患者，数百种新型治疗肽处于临床前和临床开发阶段。这一成功的关键因素是肽的有效和特异性，但安全的作用模式。在广泛的生物活性肽中，天然存在的海洋衍生的环多肽表现出广泛的不寻常的和有效的药理活性。由于其大小和复杂性，富含脯氨酸的环肽（PRCP）在药物发现中占据了至关重要的化学空间，可以为调节更具挑战性的生物靶点（例如蛋白质-蛋白质相互作用和变构结合位点）提供有用的支架。来自海绵、被囊动物和蓝细菌的天然环肽的不同药理活性鼓励了利用众所周知的合成方法（包括肽合成的固相和液相技术）开发环肽的努力。本文综述了海洋来源的富含脯氨酸的多肽的天然资源、独特的结构特征和最相关的生物学特性，重点介绍了PRCPs作为一种有前途的基于多肽的新型药物来源可能发挥的潜在治疗作用。
Peptides have gained increased interest as therapeutics during recent years. More than 60 peptide drugs have reached the market for the benefit of patients and several hundreds of novel therapeutic peptides are in preclinical and clinical development. The key contributor to this success is the potent and specific, yet safe, mode of action of peptides. Among the wide range of biologically-active peptides, naturally-occurring marine-derived cyclopolypeptides exhibit a broad range of unusual and potent pharmacological activities. Because of their size and complexity, proline-rich cyclic peptides (PRCPs) occupy a crucial chemical space in drug discovery that may provide useful scaffolds for modulating more challenging biological targets, such as protein-protein interactions and allosteric binding sites. Diverse pharmacological activities of natural cyclic peptides from marine sponges, tunicates and cyanobacteria have encouraged efforts to develop cyclic peptides with well-known synthetic methods, including solid-phase and solution-phase techniques of peptide synthesis. The present review highlights the natural resources, unique structural features and the most relevant biological properties of proline-rich peptides of marine-origin, focusing on the potential therapeutic role that the PRCPs may play as a promising source of new peptide-based novel drugs.
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