构建多环噬菌体展示文库的策略。

IF 2.6 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
ChemBioChem Pub Date : 2024-03-11 DOI:10.1002/cbic.202400072
Dr. Fa-Jie Chen, Nicole Pinnette, Dr. Jianmin Gao
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引用次数: 0

摘要

与小分子药物和抗体药物相比,多肽疗法具有多种优势,因此备受关注。肽类药物更容易合成,具有口服生物利用度的潜力,而且肽类药物足够大,可以针对小分子药物无法解决的蛋白质与蛋白质之间的相互作用。然而,由于肽类药物代谢不稳定以及难以达到类似抗体的效价和特异性等两大局限性,开发新型肽类治疗药物变得十分困难。与线性肽和二硫单环肽相比,多环肽能提高构象刚性,增强代谢稳定性,在抑制蛋白质-蛋白质相互作用方面具有更高的效力。不过,最近在构建多环噬菌体文库方面取得的进展大大推进了为治疗相关蛋白靶点鉴定新型多环肽结合剂的进程。本综述将介绍目前用于创建多环肽文库的方法,重点介绍开发的新型化学方法以及针对不同蛋白质靶点验证这些文库的概念验证工作。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Strategies for the Construction of Multicyclic Phage Display Libraries

Strategies for the Construction of Multicyclic Phage Display Libraries

Peptide therapeutics have gained great interest due to their multiple advantages over small molecule and antibody-based drugs. Peptide drugs are easier to synthesize, have the potential for oral bioavailability, and are large enough to target protein-protein interactions that are undruggable by small molecules. However, two major limitations have made it difficult to develop novel peptide therapeutics not derived from natural products, including the metabolic instability of peptides and the difficulty of reaching antibody-like potencies and specificities. Compared to linear and disulfide-monocyclized peptides, multicyclic peptides can provide increased conformational rigidity, enhanced metabolic stability, and higher potency in inhibiting protein-protein interactions. The identification of novel multicyclic peptide binders can be difficult, however, recent advancements in the construction of multicyclic phage libraries have greatly advanced the process of identifying novel multicyclic peptide binders for therapeutically relevant protein targets. This review will describe the current approaches used to create multicyclic peptide libraries, highlighting the novel chemistries developed and the proof-of-concept work done on validating these libraries against different protein targets.

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来源期刊
ChemBioChem
ChemBioChem 生物-生化与分子生物学
CiteScore
6.10
自引率
3.10%
发文量
407
审稿时长
1 months
期刊介绍: ChemBioChem (Impact Factor 2018: 2.641) publishes important breakthroughs across all areas at the interface of chemistry and biology, including the fields of chemical biology, bioorganic chemistry, bioinorganic chemistry, synthetic biology, biocatalysis, bionanotechnology, and biomaterials. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies, and supported by the Asian Chemical Editorial Society (ACES).
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