具有抗致病真菌活性的天然植物环肽的硅学分析

IF 1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Protein and Peptide Letters Pub Date : 2024-01-01 DOI:10.2174/0109298665295545240223114346
Akshita Sharma, Bisma Butool, Pallavi Sahu, Reema Mishra, Aparajita Mohanty
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引用次数: 0

摘要

背景:植物、动物和人类中的真菌感染在全球广泛存在。用于治疗真菌感染的抗真菌药物种类有限,而且由于真菌菌株的快速进化而导致药效丧失,这给农业和卫生部门带来了挑战。因此,寻找一类新的抗真菌药物势在必行。环肽是具有多种生物活性(包括抗真菌活性)的环状植物肽。它们有六个保守的半胱氨酸残基,形成三个二硫键(CI-CIV、CII-CV、CIII-CVI),建立了环状胱氨酸结(CCK)结构,使其具有极强的抗化学、酶和热攻击能力。目的:本研究对天然植物环肽进行了硅学分析,旨在评估可帮助和加速筛选具有强效抗真菌活性的环肽的参数,并将其优先用于体内/体外实验:本研究的目的是进行硅学研究,比较实验筛选(来自文献调查)的强效(MIC ≤ 20 μM)和非强效(MIC > 20 μM)环苷酸的理化参数、序列多样性、表面结构和膜-环苷酸相互作用的抗真菌活性:从数据库(Cybase)中检索抗真菌活性评估的环肽序列。基于序列的研究使用了各种在线和离线工具,如理化参数、序列多样性和邻接树。此外,还进行了基于结构的研究,包括表面结构分析和膜-环肽相互作用。所有研究都是在硅学中进行的:结果:与非强效环化苷酸相比,强效环化苷酸的理化参数值,即等电点、净电荷和碱性氨基酸的数量明显较高。强效环苷酸的表面结构显示出更大的疏水斑块和更多的疏水氨基酸。此外,强效环苷酸的膜-环苷酸相互作用研究显示,其转移自由能(ΔG转移)较低,对真菌膜的穿透深度较高,这表明其具有较高的结合稳定性和膜破坏能力:结论:硅学研究可用于快速鉴定体内和体外实验中的潜在强效抗真菌环化物,最终将应用于农业和医药领域。
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In Silico Analysis of Natural Plant-Derived Cyclotides with Antifungal Activity against Pathogenic Fungi.

Background: Fungal infections in plants, animals, and humans are widespread across the world. Limited classes of antifungal drugs to treat fungal infections and loss of drug efficacy due to rapidly evolving fungal strains pose a challenge in the agriculture and health sectors. Hence, the search for a new class of antifungal agents is imperative. Cyclotides are cyclic plant peptides with multiple bioactivities, including antifungal activity. They have six conserved cysteine residues forming three disulfide linkages (CI-CIV, CII-CV, CIII-CVI) that establish a Cyclic Cystine Knot (CCK) structure, making them extremely resistant to chemical, enzymatic, and thermal attacks.

Aim: This in silico analysis of natural, plant-derived cyclotides aimed to assess the parameters that can assist and hasten the process of selecting the cyclotides with potent antifungal activity and prioritize them for in vivo/ in vitro experiments.

Objective: The objective of this study was to conduct in silico studies to compare the physicochemical parameters, sequence diversity, surface structures, and membrane-cyclotide interactions of experimentally screened (from literature survey) potent (MIC ≤ 20 μM) and non-potent (MIC > 20 μM) cyclotides for antifungal activity.

Methodology: Cyclotide sequences assessed for antifungal activity were retrieved from the database (Cybase). Various online and offline tools were used for sequence-based studies, such as physicochemical parameters, sequence diversity, and neighbor-joining trees. Structure-based studies involving surface structure analysis and membrane-cyclotide interaction were also carried out. All investigations were conducted in silico.

Results: Physicochemical parameter values, viz. isoelectric point, net charge, and the number of basic amino acids, were significantly higher in potent cyclotides compared to non-potent cyclotides. The surface structure of potent cyclotides showed a larger hydrophobic patch with a higher number of hydrophobic amino acids. Furthermore, the membrane-cyclotide interaction studies of potent cyclotides revealed lower transfer free energy (ΔG transfer) and higher penetration depth into fungal membranes, indicating higher binding stability and membrane-disruption ability.

Conclusion: These in silico studies can be applied for rapidly identifying putatively potent antifungal cyclotides for in vivo and in vitro experiments, which will ultimately be relevant in the agriculture and pharmaceutical sectors.

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来源期刊
Protein and Peptide Letters
Protein and Peptide Letters 生物-生化与分子生物学
CiteScore
2.90
自引率
0.00%
发文量
98
审稿时长
2 months
期刊介绍: Protein & Peptide Letters publishes letters, original research papers, mini-reviews and guest edited issues in all important aspects of protein and peptide research, including structural studies, advances in recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, and drug design. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallization and preliminary structure determination of biologically important proteins are considered only if they include significant new approaches or deal with proteins of immediate importance, and preliminary structure determinations of biologically important proteins. Purely theoretical/review papers should provide new insight into the principles of protein/peptide structure and function. Manuscripts describing computational work should include some experimental data to provide confirmation of the results of calculations. Protein & Peptide Letters focuses on: Structure Studies Advances in Recombinant Expression Drug Design Chemical Synthesis Function Pharmacology Enzymology Conformational Analysis Immunology Biotechnology Protein Engineering Protein Folding Sequencing Molecular Recognition Purification and Analysis
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