Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Bioorg Med Chem. 2018 Jun 1;26(10):2727-2737. doi: 10.1016/j.bmc.2017.08.005. Epub 2017 Aug 8.
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 PawS-derived 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.
由于其出色的稳定性和有利的药代动力学特性，植物来源的环肽最近在基于肽的药物设计领域引起了广泛关注。本文介绍了核糖体合成的植物肽的三大类 - 环肽、 PawS 衍生肽和轨道肽，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多种生物活性，包括抗 HIV、细胞毒性和免疫调节活性。此外，最近的研究重点还集中在将它们用作稳定生物活性肽序列的支架上，从而增强它们的生物制药特性。现在已经有 30 多篇关于这种“嫁接”应用的论文，其中大部分是在过去几年中报道的，并且有几项此类研究报告了口服给予的环肽的体内活性。在本文中，我们描述了环肽及其经药物修饰的衍生物的合成方法，并概述了它们的生物合成途径。最后，我们描述了涉及植物和植物悬浮培养物的具有药用活性的环肽的可能生物生产途径。
