Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, Rome, Italy.
J Pept Sci. 2011 May;17(5):335-41. doi: 10.1002/psc.1340. Epub 2011 Feb 4.
Cell-penetrating peptides (CPPs) are cationic oligopeptides able to translocate across biological membranes without perturbing them, while antimicrobial peptides (AMPs) kill bacteria mainly by disrupting their membranes. The two peptide classes share several characteristics (charge, amphipathicity, helicity, and length), and therefore the molecular properties discriminating between the two different bioactivities are not clear. Pep-1-K (KKTWWKTWWTKWSQPKKKRKV) is a new AMP derived from the widely studied CPP Pep-1 (KETWWETWWTEWSQPKKKRKV), or 'Chariot', known for its ability to carry large cargoes across biological membranes. Pep-1-K was obtained from Pep-1 by substituting the three Glu residues with Lys, to increase its cationic character. Previous studies showed that these modifications endow Pep-1-K with a potent antimicrobial activity, with MICs in the low micromolar range. Here, we characterized the interaction of Pep-1 and Pep-1-K with model membranes to understand the reason for the antimicrobial activity of Pep-1-K. The data show that this peptide causes vesicle aggregation, perturbs membrane order, and induces the leakage of ions, but not of larger solutes, while these effects were not observed for Pep-1. These differences are likely due, at least in part, to the higher affinity of Pep-1-K toward anionic bilayers, which mimick the composition of bacterial membranes.
细胞穿透肽（CPPs）是一种阳离子寡肽，能够穿透生物膜而不破坏它们，而抗菌肽（AMPs）主要通过破坏它们的膜来杀死细菌。这两类肽具有一些共同的特征（电荷、两亲性、螺旋性和长度），因此，区分这两种不同生物活性的分子特性尚不清楚。Pep-1-K（KKTWWKTWWTKWSQPKKKRKV）是一种新的 AMP，来源于广泛研究的 CPP Pep-1（KETWWETWWTEWSQPKKKRKV），也称为“Chariot”，因其能够携带大分子物质穿过生物膜而闻名。Pep-1-K 通过将三个 Glu 残基替换为 Lys，增加了其正电荷性质，从而获得。先前的研究表明，这些修饰使 Pep-1-K 具有强大的抗菌活性，MIC 值在低微摩尔范围内。在这里，我们研究了 Pep-1 和 Pep-1-K 与模型膜的相互作用，以了解 Pep-1-K 抗菌活性的原因。数据表明，这种肽会引起囊泡聚集，扰乱膜的有序性，并诱导离子泄漏，但不会引起较大溶质的泄漏，而 Pep-1 则没有观察到这些效应。这些差异可能至少部分归因于 Pep-1-K 与阴离子双层的亲和力更高，而阴离子双层模拟了细菌膜的组成。
