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蛙皮抗菌肽:生物多样性与治疗潜力。

Antimicrobial peptides from frog skin: biodiversity and therapeutic promises.

机构信息

Sorbonne Universités, UPMC Univ Paris 06, CNRS, Institut de Biologie Paris Seine (IBPS, FR 3631), Biogenèse des Signaux Peptidiques (BIOSIPE), F-75005, Paris, France,

Sorbonne Universités, UPMC Univ Paris 06, F-75005, Paris, France.

出版信息

Front Biosci (Landmark Ed). 2016 Jun 1;21(7):1341-71. doi: 10.2741/4461.

Abstract

More than a thousand antimicrobial peptides (AMPs) have been reported in the last decades arising from the skin secretion of amphibian species. Generally, each frog species can express its own repertoire of AMPs (typically, 10-20 peptides) with differing sequences, sizes, and spectrum of action, which implies very rapid divergence, even between closely related species. Frog skin AMPs are highly potent against antibiotic-resistant bacteria, protozoa, yeasts, and fungi by permeating and destroying their plasma membrane and/or inactivating intracellular targets. These peptides have attracted considerable interest as a therapeutic alternative to conventional anti-infective agents. However, efforts to obtain a new generation of drugs using these peptides are still challenging because of high associated R&D costs due to their large size (up to 46 residues) and cytotoxicity. This review deals with the biodiversity of frog skin AMPs and assesses the therapeutic possibilities of temporins, the shortest AMPs found in the frog skin, with 8-17 residues. Such short sequences are easily amenable to optimization of the structure and to solution-phase synthesis that offer reduced costs over solid-phase chemistry.

摘要

在过去的几十年中,已经从两栖动物的皮肤分泌物中发现了一千多种抗菌肽 (AMPs)。一般来说,每个青蛙物种都可以表达自己的 AMP 库(通常为 10-20 种肽),具有不同的序列、大小和作用谱,这意味着即使是亲缘关系密切的物种之间也存在着非常快速的分化。青蛙皮肤 AMPs 通过渗透和破坏其质膜和/或使细胞内靶标失活,对对抗生素耐药细菌、原生动物、酵母和真菌具有高度的活性。这些肽作为传统抗感染药物的替代治疗方法引起了极大的关注。然而,由于其较大的尺寸(高达 46 个残基)和细胞毒性,使用这些肽获得新一代药物的努力仍然具有挑战性。本文综述了青蛙皮肤 AMPs 的生物多样性,并评估了在青蛙皮肤中发现的最短的 AMPs—— temporins 的治疗潜力,其长度为 8-17 个残基。这种短序列易于优化结构,易于在溶液相中合成,与固相化学相比降低了成本。

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