Ribosomally-synthesised cyclic peptides from plants as drug leads and pharmaceutical scaffolds
Ribosomally-synthesised cyclic peptides from plants as drug leads and pharmaceutical scaffolds
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DOI：
10.1016/j.bmc.2017.08.005
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发表时间：
2018-06-01
影响因子：
3.5
通讯作者：
Peacock, Hayden
中科院分区：
文献类型：
--
作者：
Craik, David J.;Lee, Meng-Han;Peacock, Hayden
由于其优异的稳定性和良好的药代动力学特性，植物源性环肽近年来在肽类药物设计领域引起了极大的关注。本文介绍了核糖体合成的植物肽的三大类——环肽、PawSderived肽和轨道肽，并综述了它们作为先导物或支架在药物设计中的应用。这些核糖体产生的肽具有一系列的生物活性，包括抗hiv、细胞毒性和免疫调节活性。此外，最近的兴趣集中在它们作为支架来稳定生物活性肽序列，从而提高它们的生物制药性能。目前已经发表了30多篇关于这种“嫁接”应用的论文，其中大多数是最近几年才报道的，并且有几篇这样的研究报道了口服环肽的体内活性。在这篇文章中，我们描述了合成环肽及其药物接枝衍生物的方法，并概述了它们的生物合成路线。最后，我们描述了可能的生物生产途径的药物活性环肽，涉及植物和植物悬浮培养。(C) 2017 Elsevier Ltd.版权所有。
Owing to their exceptional stability and favourable pharmacokinetic properties, plant-derived cyclic peptides have recently attracted significant attention in the field of peptide-based drug design. This article describes the three major classes of ribosomally-synthesised plant peptides - the cyclotides, the PawSderived peptides and the orbitides -and reviews their applications as leads or scaffolds in drug design. These ribosomally-produced peptides have a range of biological activities, including anti-HIV, cytotoxic and immunomodulatory activity. In addition, recent interest has focused on their use as scaffolds to stabilise bioactive peptide sequences, thereby enhancing their biopharmaceutical properties. There are now more than 30 published papers on such 'grafting' applications, most of which have been reported only in the last few years, and several such studies have reported in vivo activity of orally delivered cyclic peptides. In this article, we describe approaches to the synthesis of cyclic peptides and their pharmaceutically-grafted derivatives as well as outlining their biosynthetic routes. Finally, we describe possible bioproduction routes for pharmaceutically active cyclic peptides, involving plants and plant suspension cultures. (C) 2017 Elsevier Ltd. All rights reserved.