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Development and Challenges of Antimicrobial Peptides for Therapeutic Applications

机译:用于治疗应用的抗菌肽的发展和挑战

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摘要

More than 3000 antimicrobial peptides (AMPs) have been discovered, seven of which have been approved by the U.S. Food and Drug Administration (FDA). Now commercialized, these seven peptides have mostly been utilized for topical medications, though some have been injected into the body to treat severe bacterial infections. To understand the translational potential for AMPs, we analyzed FDA-approved drugs in the FDA drug database. We examined their physicochemical properties, secondary structures, and mechanisms of action, and compared them with the peptides in the AMP database. All FDA-approved AMPs were discovered in Gram-positive soil bacteria, and 98% of known AMPs also come from natural sources (skin secretions of frogs and toxins from different species). However, AMPs can have undesirable properties as drugs, including instability and toxicity. Thus, the design and construction of effective AMPs require an understanding of the mechanisms of known peptides and their effects on the human body. This review provides an overview to guide the development of AMPs that can potentially be used as antimicrobial drugs.
机译:已发现3000多种抗菌肽(AMP),其中7种已获得美国食品药品监督管理局(FDA)的批准。现在已商业化,这七个肽已被大部分用于局部药物治疗,尽管其中一些已被注射到体内以治疗严重的细菌感染。为了了解AMPs的翻译潜力,我们在FDA药物数据库中分析了FDA批准的药物。我们检查了它们的理化性质,二级结构和作用机理,并将其与AMP数据库中的肽进行了比较。所有FDA批准的AMPs都在革兰氏阳性土壤细菌中发现,并且98%的已知AMPs也来自自然资源(青蛙的皮肤分泌物和不同物种的毒素)。但是,AMPs作为药物可能具有不良的特性,包括不稳定和毒性。因此,有效AMP的设计和构建需要了解已知肽的机理及其对人体的影响。这篇综述提供了概述,以指导可能用作抗菌药物的AMP的开发。

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