Bismuth-Cyclized Cell-Penetrating Peptides

IF 4.5 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Molecular Pharmaceutics Pub Date : 2024-09-02 DOI:10.1021/acs.molpharmaceut.4c0068810.1021/acs.molpharmaceut.4c00688
Jeremy L. Ritchey, Lindsi Filippi, Davis Ballard and Dehua Pei*, 
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Abstract

Intracellular delivery of biological cargos, which would yield new research tools and novel therapeutics, remains an active area of research. A convenient and potentially general approach involves the conjugation of a cell-penetrating peptide to a cargo of interest. However, linear CPPs lack sufficient cytosolic entry efficiency and metabolic stability, while previous backbone cyclized CPPs have several drawbacks including the necessity for chemical synthesis and posttranslational conjugation to peptide/protein cargos and epimerization during cyclization. We report here a new class of bismuth cyclized CPPs with excellent cytosolic entry efficiencies, proteolytic stability, and potential compatibility with genetic encoding and recombinant production.

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铋环化细胞穿透肽
生物载体的细胞内递送将产生新的研究工具和新型疗法,这仍然是一个活跃的研究领域。一种方便且可能通用的方法是将细胞穿透肽与感兴趣的载体共轭。然而,线性 CPP 缺乏足够的细胞进入效率和代谢稳定性,而以前的骨架环化 CPP 有几个缺点,包括必须进行化学合成和翻译后与肽/蛋白载体连接,以及在环化过程中发生二聚化。我们在此报告了一类新的铋环化 CPPs,它们具有出色的细胞膜进入效率、蛋白水解稳定性以及与基因编码和重组生产的潜在兼容性。
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来源期刊
Molecular Pharmaceutics
Molecular Pharmaceutics 医学-药学
CiteScore
8.00
自引率
6.10%
发文量
391
审稿时长
2 months
期刊介绍: Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development. Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.
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