Department of Chemistry and Ilse Katz Institute for Nanotechnology, Ben Gurion University, Beer Sheva 84105, Israel.
J Phys Chem B. 2010 Sep 2;114(34):11053-60. doi: 10.1021/jp1052248.
Novicidin is an antimicrobial peptide derived from ovispirin, a cationic peptide which originated from the ovine cathelicidin SMAP-29. Novicidin, however, has been designed to minimize the cytotoxic properties of SMAP-29 and ovisipirin toward achieving potential therapeutic applications. We present an analysis of membrane interactions and lipid bilayer penetration of novicidin, using an array of biophysical techniques and biomimetic membrane assemblies, complemented by Monte Carlo (MC) simulations. The data indicate that novicidin interacts minimally with zwitterionic bilayers, accounting for its low hemolytic activity. Negatively charged phosphatidylglycerol, on the other hand, plays a significant role in initiating membrane binding of novicidin, and promotes peptide insertion into the interface between the lipid headgroups and the acyl chains. The significant insertion into bilayers containing negative phospholipids might explain the enhanced antibacterial properties of novicidin. Overall, this study highlights two distinct outcomes for membrane interactions of novicidin, and points to a combination between electrostatic attraction to the lipid/water interface and penetration into the subsurface lipid headgroups region as important determinants for the biological activity of novicidin.
诺维西丁是一种抗菌肽，来源于绵羊素，这是一种源于绵羊抗菌肽 SMAP-29 的阳离子肽。然而，诺维西丁的设计目的是尽量减少 SMAP-29 和绵羊素的细胞毒性，以实现潜在的治疗应用。我们使用一系列生物物理技术和仿生膜组件，以及蒙特卡罗（MC）模拟，对诺维西丁的膜相互作用和脂质双层渗透进行了分析。数据表明，诺维西丁与两性离子双层的相互作用最小，这解释了它的低溶血活性。另一方面，带负电荷的磷脂酰甘油在启动诺维西丁与膜的结合方面起着重要作用，并促进肽插入脂质头部基团和酰基链之间的界面。在含有负电荷磷脂的双层中显著插入可能解释了诺维西丁增强的抗菌特性。总的来说，这项研究突出了诺维西丁与膜相互作用的两种截然不同的结果，并指出静电吸引到脂质/水界面和穿透到亚表面脂质头部基团区域的结合是诺维西丁生物学活性的重要决定因素。
