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套索肽领域:见解与应用

Lasso peptides realm: Insights and applications.

作者信息

Al Musaimi Othman

机构信息

School of Pharmacy, Newcastle University, Newcastle upon Tyne UK NE1 7RU, UK; Department of Chemical Engineering, Imperial College London, London SW7 2AZ, UK.

出版信息

Peptides. 2024 Dec;182:171317. doi: 10.1016/j.peptides.2024.171317. Epub 2024 Nov 1.

Abstract

Lasso peptides exhibit a range of bioactivities, including antiviral effects, inhibition of the glucagon receptor, blockade of the endothelin type B receptor, inhibition of myosin light chain kinase, and modulation of the atrial natriuretic factor, as well as notable antimicrobial properties. Intriguingly, lasso peptides exhibit remarkable proteolytic and thermal stability, addressing one of the key challenges that traditional peptides often face. The challenge in producing those valuable peptides remains the main hurdle in the way of producing larger quantities or even modifying them with more potent analogues. Genome mining and heterologous expression approaches have greatly facilitated the production of lasso peptides, moving beyond mere isolation techniques. This advancement not only allows for larger quantities but also enables the creation of additional analogues with improved stability and potency. This review aims to explore the unique bioactivities and stability of lasso peptides, along with recent advancements in genome mining and heterologous expression that address production challenges and open pathways for engineering potent analogues.

摘要

套索肽具有一系列生物活性,包括抗病毒作用、抑制胰高血糖素受体、阻断内皮素B型受体、抑制肌球蛋白轻链激酶以及调节心房利钠因子,还具有显著的抗菌特性。有趣的是,套索肽表现出卓越的蛋白水解稳定性和热稳定性,解决了传统肽常常面临的关键挑战之一。生产这些有价值的肽所面临的挑战仍然是大量生产甚至用更有效的类似物对其进行修饰的主要障碍。基因组挖掘和异源表达方法极大地促进了套索肽的生产,超越了单纯的分离技术。这一进展不仅能够实现大量生产,还能创造出具有更高稳定性和效力的其他类似物。本综述旨在探讨套索肽独特的生物活性和稳定性,以及基因组挖掘和异源表达方面的最新进展,这些进展解决了生产挑战,并为设计高效类似物开辟了途径。

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