Mechanisms Inspired Targeting Peptides
Mechanisms Inspired Targeting Peptides
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靶向肽的启发机制
DOI：
10.1007/978-981-15-3266-5_21
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发表时间：
2020
影响因子：
--
通讯作者：
袁运生
中科院分区：
文献类型：
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作者：
袁运生
肽作为一大类分子，由氨基酸残基组成，根据结构可分为直链或环状肽。已经发现了超过13，000种天然肽分子，其中许多已经得到了很好的研究。在人工肽库中，肽多样性最高可达1 × 1013。与小分子化合物相比，多肽具有更复杂的结构和更高的亲和力。近年来，靶向肿瘤免疫检查点（CIP）抑制剂的开发在肿瘤治疗中发挥着重要作用。CIP中的肽靶向配体或受体已经基于靶蛋白的三维结构设计或通过生物展示系统中的随机肽库直接选择。这些靶向肽中的大多数都作为蛋白质-蛋白质相互作用的抑制剂发挥作用，并改善肿瘤微环境中CD 8+细胞毒性T淋巴细胞（CTL）的激活，例如PKHB 1、Ar 5 Y 4和TPP 1。可以设计肽来调节CIP蛋白在体内的降解，例如PD-LYSO和PD-PALM。靶向肽除了可用于开发靶向CIP的治疗药物外，还可用于肿瘤免疫治疗中的药物靶向给药和诊断。
Peptides, as a large group of molecules, are composed of amino acid residues and can be divided into linear or cyclic peptides according to the structure. Over 13,000 molecules of natural peptides have been found and many of them have been well studied. In artificial peptide libraries, the number of peptide diversity could be up to 1 × 1013. Peptides have more complex structures and higher affinity to target proteins comparing with small molecular compounds. Recently, the development of targeting cancer immune checkpoint (CIP) inhibitors is having a very important role in tumor therapy. Peptides targeting ligands or receptors in CIP have been designed based on three-dimensional structures of target proteins or directly selected by random peptide libraries in biological display systems. Most of these targeting peptides work as inhibitors of protein–protein interaction and improve CD8+ cytotoxic T-lymphocyte (CTL) activation in the tumor microenvironment, for example, PKHB1, Ar5Y4 and TPP1. Peptides could be designed to regulate CIP protein degradation in vivo, such as PD-LYSO and PD-PALM. Besides its use in developing therapeutic drugs for targeting CIP, targeting peptides could be used in drug’s targeted delivery and diagnosis in tumor immune therapy.