期刊
PHARMACEUTICAL RESEARCH
卷 28, 期 11, 页码 2797-2807出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-011-0493-7
关键词
cationic amphiphilic polyproline helices; cell penetrating peptides; dimerization; mitochondrial targeting
资金
- Direct For Mathematical & Physical Scien
- Division Of Chemistry [1012316] Funding Source: National Science Foundation
Efficient delivery of therapeutic biopolymers across cell membranes remains a daunting challenge. The development of cell-penetrating peptides (CPPs) has been useful; however, many CPPs are found trapped within endosomes, limiting their use as delivery agents. We optimize a class of CPPs, cationic amphiphilic polyproline helices (CAPHs), for direct transport into cells with mitochondrial localization through dimerization. The CAPH P11LRR used for this study has been found to enter cells by two distinct pathways: an endocytotic pathway was favored at low concentrations; internalization by direct transport was observed at higher concentrations. CAPH was dimerized to probe if direct transport within cells may be enhanced through increased association of CAPH with the membrane and through the association of individual peptides within the membrane. The dimerization of the CAPH was found to significantly increase cellular uptake over its monomeric counterpart, with a concomitant lowering of the concentration threshold favoring direct transport. Evidence for direct transport within cells and mitochondrial localization was observed. CAPH cellular uptake efficiency can be significantly enhanced through peptide dimerization while favoring cell entry via direct transport at low concentration with low cell toxicity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据