[论文解读] Transmembrane and Antimicrobial Peptides. Hydrophobicity, Amphiphilicity and Propensity to Aggregation

Malak Pirtskhalava, Boris Vishnepolsky+1 more|arXiv (Cornell University)|Jul 23, 2013

Antimicrobial Peptides and Activities参考文献 127被引用 12

一句话总结

本综述分析了疏水性、两亲性和聚集倾向作为区分抗菌肽（AMPs）与跨膜肽的关键理化性质。研究表明，尽管两类肽均依赖这些特性实现与膜的相互作用，AMPs 展现出独特的聚集偏倚和两亲性模式，从而实现膜破坏，为设计新型抗耐药病原体的抗菌剂提供了设计原则。

ABSTRACT

Development of the new antimicrobial agents against antibiotic resistance pathogens is the nowadays challenge. Antimicrobial peptides (AMP) occur as important defence agents in many organisms and offer a viable alternative to conventional antibiotics. Therefore they have become increasingly recognized in current research as templates for prospective antibiotic agents. The efficient designing of the new antimicrobials on the basis of antimicrobial peptides requires comprehensive knowledge on those general physical-chemical characteristics which allow to differ antimicrobial peptides from non-active against microbs ones. According to supposed mechanisms of action, AMP interact with and physically disrupt the bacterial membranes. Consequently, hydrophobicity, amphiphilicity and intrinsic aggregation propensities are considered as such major characteristics of the peptide, which determine the results of peptide-membrane interactions. For some kind of peptides such characteristics as hydrophobicity, amphiphilicity and aggregation bias determines their ability to compose transmembrane domain of the membrane protein, whilst for others the same properties are respond for their antimicrpobial activity, i.e. give them ability of membrane permeability and its damage. In this review we analyze the data about hydrophobicity, amphiphilicity and intrinsic aggregation propensities available in literature in order to compare antimicrobial and transmembrane peptides and show what is the common and what is the difference in this respect between them.

研究动机与目标

• 识别区分抗菌肽（AMPs）与跨膜肽的理化特性。
• 理解疏水性、两亲性和内在聚集倾向如何影响肽-膜相互作用。
• 阐明这些性质在膜插入和破坏中的共性和差异作用。
• 基于AMP模板，为理性设计新型抗菌剂提供框架。
• 评估AMPs作为传统抗生素替代品的潜力，以应对日益严重的抗生素耐药性问题。

提出的方法

• 系统性回顾关于肽中疏水性、两亲性和聚集倾向的文献。
• 利用理化参数对比分析跨膜肽与抗菌肽。
• 评估疏水偶极矩和残基分布等肽结构特征。
• 通过基于序列的预测模型评估内在聚集倾向。
• 整合有关膜相互作用机制的数据，包括孔道形成和双分子层破坏。
• 运用既定的物理化学原理，将肽的理化性质与生物功能相关联。

实验结果

研究问题

• RQ1 哪些理化性质能够区分抗菌肽与跨膜肽？
• RQ2 疏水性和两亲性在AMPs的膜插入和破坏中发挥何种作用？
• RQ3 内在聚集倾向在多大程度上影响抗菌肽的活性？
• RQ4 疏水性和两亲性在AMPs与跨膜肽中的作用有何异同？
• RQ5 能否通过调控AMPs的聚集行为来增强其治疗潜力？

主要发现

• 疏水性和两亲性对跨膜肽和抗菌肽的功能均至关重要，可促进与膜的结合。
• 与跨膜肽相比，抗菌肽具有更高的自聚集倾向，这可能有助于孔道的形成。
• 具有疏水面和亲水面分离的两亲性结构是AMPs实现膜破坏的关键决定因素。
• 疏水性与两亲性的平衡影响肽插入并破坏脂质双分子层的能力。
• 内在聚集倾向在AMPs中更为显著，且与形成孔道或破坏膜的能力密切相关。
• 尽管具有共同的理化特性，AMPs与跨膜肽在调控其生物活性的特定序列模式和聚集动力学方面存在差异。