Efficient Delivery of Macromolecules into Human Cells by Improving the Endosomal Escape Activity of Cell-Penetrating Peptides: Lessons Learned from dfTAT and its Analogs

被引:39
作者
Allen, Jason K. [1 ]
Brock, Dakota J. [1 ]
Kondow-McConaghy, Helena M. [1 ]
Pellois, Jean-Philippe [1 ,2 ]
机构
[1] Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA
[2] Texas A&M Univ, Dept Chem, College Stn, TX 77845 USA
来源
BIOMOLECULES | 2018年 / 8卷 / 03期
关键词
peptide; cell-penetrating peptide; cellular delivery; endosomal escape; membrane leakage; TAT peptide; multimerization; chirality; charge density; HUMAN IMMUNODEFICIENCY VIRUS; LIVE CELLS; TAT PROTEIN; MEMBRANE; INTERNALIZATION; RELEASE; MECHANISMS; NUCLEUS; DOMAINS; AGENT;
D O I
10.3390/biom8030050
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cell-penetrating peptides (CPPs) are typically prone to endocytic uptake into human cells. However, they are often inefficient at escaping from endosomes, which limits their ability to deliver cargos into cells. This review highlights the efforts that our laboratory has devoted toward developing CPPs that can mediate the leakage of endosomal membranes, and consequently gain better access to the intracellular milieu. In particular, we have identified a CPP named dimeric fluorescent TAT (dfTAT) with high endosomolytic activity. We describe how we have used this reagent and its analogs to develop efficient cytosolic delivery protocols and learn about molecular and cellular parameters that control the cell permeation process. Specifically, we discuss how late endosomes represent exploitable gateways for intracellular entry. We also describe how certain features in CPPs, including guanidinium content, charge density, multimerization, chirality, and susceptibility to degradation modulate the activity that these peptidic agents take toward endosomal membranes and cytosolic egress.
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页数:13
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