Almeida Paulo F, Pokorny Antje
Department of Chemistry and Biochemistry, University of North Carolina Wilmington, North Carolina 28403, USA.
Biochemistry. 2009 Sep 1;48(34):8083-93. doi: 10.1021/bi900914g.
The mechanisms of six different antimicrobial, cytolytic, and cell-penetrating peptides, including some of their variants, are discussed and compared. The specificity of these polypeptides varies; however, they all form amphipathic alpha-helices when bound to membranes, and there are no striking differences in their sequences. We have examined the thermodynamics and kinetics of their interaction with phospholipid vesicles, namely, binding and peptide-induced dye efflux. The thermodynamics of binding calculated using the Wimley-White interfacial hydrophobicity scale are in good agreement with the values derived from experiment. The generally accepted view that binding affinity determines functional specificity is also supported by experiments in model membranes. We now propose the hypothesis that it is the thermodynamics of the insertion of the peptide into the membrane, from a surface-bound state, that determine the mechanism.
本文讨论并比较了六种不同的抗菌、溶细胞和细胞穿透肽及其一些变体的作用机制。这些多肽的特异性各不相同；然而，它们在与膜结合时均形成两亲性α螺旋，且序列上没有显著差异。我们研究了它们与磷脂囊泡相互作用的热力学和动力学，即结合和肽诱导的染料外排。使用Wimley-White界面疏水性标度计算的结合热力学与实验得出的值高度一致。结合亲和力决定功能特异性这一普遍接受的观点也得到了模型膜实验的支持。我们现在提出一个假设，即从表面结合状态将肽插入膜的热力学决定了其作用机制。
