Department of Biochemistry, Kansas State University, Manhattan, KS 66506, USA.
Biochimie. 2010 Sep;92(9):1236-41. doi: 10.1016/j.biochi.2010.02.023. Epub 2010 Feb 25.
Antimicrobial host defense peptides (HDPs) are a critical component of the innate immunity with microbicidal, endotoxin-neutralizing, and immunostimulatory properties. HDPs kill bacteria primarily through non-specific membrane lysis, therefore with a less likelihood of provoking resistance. Extensive structure-activity relationship studies with a number of HDPs have revealed that net charge, amphipathicity, hydrophobicity, and structural propensity are among the most important physicochemical and structural parameters that dictate their ability to interact with and disrupt membranes. A delicate balance among these factors, rather than a mere alteration of a single factor, is critically important for HDPs to ensure the antimicrobial potency and target cell selectivity. With a better understanding of the structural determinants of HDPs for their membrane-lytic activities, it is expected that novel HDP-based antimicrobials with minimum toxicity to eukaryotic cells can be developed for resistant infections, which have become a global public health crisis.
抗菌宿主防御肽（HDPs）是先天免疫的重要组成部分，具有杀菌、中和内毒素和免疫刺激特性。HDPs 主要通过非特异性膜裂解杀死细菌，因此不太可能引发耐药性。对许多 HDP 进行的广泛结构-活性关系研究表明，净电荷、两亲性、疏水性和结构倾向是决定其与膜相互作用和破坏膜能力的最重要的物理化学和结构参数之一。这些因素之间的微妙平衡，而不仅仅是单一因素的改变，对于 HDP 确保抗菌效力和靶细胞选择性至关重要。随着对 HDP 膜裂解活性的结构决定因素的更好理解，预计可以开发出新型基于 HDP 的抗菌药物，对真核细胞的毒性最小，用于治疗已成为全球公共卫生危机的耐药感染。
