A Critical Review of Short Antimicrobial Peptides from Scorpion Venoms, Their Physicochemical Attributes, and Potential for the Development of New Drugs.

IF 2.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Membrane Biology Pub Date : 2024-08-01 Epub Date: 2024-07-11 DOI:10.1007/s00232-024-00315-2
Pedro Alejandro Fong-Coronado, Verónica Ramirez, Verónica Quintero-Hernández, Daniel Balleza
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Abstract

Scorpion venoms have proven to be excellent sources of antimicrobial agents. However, although many of them have been functionally characterized, they remain underutilized as pharmacological agents, despite their evident therapeutic potential. In this review, we discuss the physicochemical properties of short scorpion venom antimicrobial peptides (ssAMPs). Being generally short (13-25 aa) and amidated, their proven antimicrobial activity is generally explained by parameters such as their net charge, the hydrophobic moment, or the degree of helicity. However, for a complete understanding of their biological activities, also considering the properties of the target membranes is of great relevance. Here, with an extensive analysis of the physicochemical, structural, and thermodynamic parameters associated with these biomolecules, we propose a theoretical framework for the rational design of new antimicrobial drugs. Through a comparison of these physicochemical properties with the bioactivity of ssAMPs in pathogenic bacteria such as Staphylococcus aureus or Acinetobacter baumannii, it is evident that in addition to the net charge, the hydrophobic moment, electrostatic energy, or intrinsic flexibility are determining parameters to understand their performance. Although the correlation between these parameters is very complex, the consensus of our analysis suggests that there is a delicate balance between them and that modifying one affects the rest. Understanding the contribution of lipid composition to their bioactivities is also underestimated, which suggests that for each peptide, there is a physiological context to consider for the rational design of new drugs.

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蝎子毒液中短抗菌肽及其理化特性和新药开发潜力的重要综述》。
事实证明,蝎毒是抗菌剂的绝佳来源。然而,尽管其中许多蝎子毒液已被确定了功能特性,但它们作为药剂的利用率仍然很低,尽管它们具有明显的治疗潜力。在这篇综述中,我们讨论了短蝎毒抗菌肽(ssAMPs)的理化性质。短蝎毒抗菌肽一般都很短(13-25 aa),而且是酰胺化的,因此它们被证实具有的抗菌活性通常可以用其净电荷、疏水力矩或螺旋度等参数来解释。然而,要全面了解它们的生物活性,还必须考虑目标膜的特性。在此,通过对与这些生物大分子相关的物理化学、结构和热力学参数的广泛分析,我们提出了合理设计新型抗菌药物的理论框架。通过将这些理化特性与 ssAMPs 在金黄色葡萄球菌或鲍曼不动杆菌等病原菌中的生物活性进行比较,我们发现除了净电荷外,疏水力矩、静电能或内在柔性也是了解其性能的决定性参数。虽然这些参数之间的相关性非常复杂,但我们的分析一致表明,它们之间存在微妙的平衡,改变其中一个参数会影响其他参数。脂质成分对其生物活性的影响也被低估了,这表明对于每种多肽,在合理设计新药时都需要考虑其生理背景。
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来源期刊
Journal of Membrane Biology
Journal of Membrane Biology 生物-生化与分子生物学
CiteScore
4.80
自引率
4.20%
发文量
63
审稿时长
6-12 weeks
期刊介绍: The Journal of Membrane Biology is dedicated to publishing high-quality science related to membrane biology, biochemistry and biophysics. In particular, we welcome work that uses modern experimental or computational methods including but not limited to those with microscopy, diffraction, NMR, computer simulations, or biochemistry aimed at membrane associated or membrane embedded proteins or model membrane systems. These methods might be applied to study topics like membrane protein structure and function, membrane mediated or controlled signaling mechanisms, cell-cell communication via gap junctions, the behavior of proteins and lipids based on monolayer or bilayer systems, or genetic and regulatory mechanisms controlling membrane function. Research articles, short communications and reviews are all welcome. We also encourage authors to consider publishing ''negative'' results where experiments or simulations were well performed, but resulted in unusual or unexpected outcomes without obvious explanations. While we welcome connections to clinical studies, submissions that are primarily clinical in nature or that fail to make connections to the basic science issues of membrane structure, chemistry and function, are not appropriate for the journal. In a similar way, studies that are primarily descriptive and narratives of assays in a clinical or population study are best published in other journals. If you are not certain, it is entirely appropriate to write to us to inquire if your study is a good fit for the journal.
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