Recent Advances in Non-Standard Macrocyclic Peptide Ligand Discovery using mRNA Display

IF 2.3 4区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY Israel Journal of Chemistry Pub Date : 2024-03-13 DOI:10.1002/ijch.202300167
Yizhen Yin, Christopher John Hipolito
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Abstract

Advancements in platform technologies have facilitated the production of libraries consisting of macrocyclic peptides composed of natural and non-canonical amino acids for more drug-like characteristics. Identification of macrocyclic peptide ligands against targets of interest can be accomplished using mRNA display. Despite numerous successful in vitro selections for macrocyclic peptide ligands against extracellular targets, identifying macrocyclic peptide hits that can reach intracellular targets continue to be a challenge. Breakthroughs in defining the features of a macrocyclic peptide that promote cell permeability have recently been disclosed. Here, we review the successful selections of non-standard macrocyclic peptide ligands using mRNA display in the last five years and chemical optimization of a drug-like macrocyclic peptide ligand for targeting intracellular KRAS.

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利用 mRNA 显示发现非标准大环肽配体的最新进展
平台技术的进步促进了由天然和非典型氨基酸组成的大环肽库的生产,使其具有更多类似药物的特性。利用 mRNA 显示技术,可以识别针对感兴趣靶点的大环肽配体。尽管体外筛选针对细胞外靶点的大环肽配体取得了许多成功,但识别能到达细胞内靶点的大环肽仍然是一项挑战。最近,在确定促进细胞渗透性的大环肽特征方面取得了突破性进展。在此,我们回顾了过去五年中利用 mRNA 展示成功筛选出的非标准大环肽配体,以及针对细胞内 KRAS 的类药物大环肽配体的化学优化。
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来源期刊
Israel Journal of Chemistry
Israel Journal of Chemistry 化学-化学综合
CiteScore
6.20
自引率
0.00%
发文量
62
审稿时长
6-12 weeks
期刊介绍: The fledgling State of Israel began to publish its scientific activity in 1951 under the general heading of Bulletin of the Research Council of Israel, which quickly split into sections to accommodate various fields in the growing academic community. In 1963, the Bulletin ceased publication and independent journals were born, with Section A becoming the new Israel Journal of Chemistry. The Israel Journal of Chemistry is the official journal of the Israel Chemical Society. Effective from Volume 50 (2010) it is published by Wiley-VCH. The Israel Journal of Chemistry is an international and peer-reviewed publication forum for Special Issues on timely research topics in all fields of chemistry: from biochemistry through organic and inorganic chemistry to polymer, physical and theoretical chemistry, including all interdisciplinary topics. Each topical issue is edited by one or several Guest Editors and primarily contains invited Review articles. Communications and Full Papers may be published occasionally, if they fit with the quality standards of the journal. The publication language is English and the journal is published twelve times a year.
期刊最新文献
Cover Picture: (Isr. J. Chem. 8-9/2024) Special Issue on RNA-Based Catalysts that Revolutionized the Discovery of Bioactive Peptides Hexagonal and Trigonal Quasiperiodic Tilings Breaking the Degeneracy of Sense Codons – How Far Can We Go? Cover Picture: (Isr. J. Chem. 6-7/2024)
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