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
相关论文
共 40 条
[1]   Generation of Endosomolytic Reagents by Branching of Cell-Penetrating Peptides: Tools for the Delivery of Bioactive Compounds to Live Cells in Cis or Trans [J].
Angeles-Boza, Alfredo M. ;
Erazo-Oliveras, Alfredo ;
Lee, Ya-Jung ;
Pellois, Jean-Philippe .
BIOCONJUGATE CHEMISTRY, 2010, 21 (12) :2164-2167
[2]   Enhanced membrane pore formation by Multimeric/Oligomeric antimicrobial peptides [J].
Arnusch, Christopher J. ;
Branderhorst, Hilbert ;
De Kruijff, Ben ;
Liskamp, Rob M. J. ;
Breukink, Eefjan ;
Pieters, Roland J. .
BIOCHEMISTRY, 2007, 46 (46) :13437-13442
[3]   Endosomal proteolysis of internalized proteins [J].
Authier, F ;
Posner, BI ;
Bergeron, JJM .
FEBS LETTERS, 1996, 389 (01) :55-60
[4]   Efficient cell delivery mediated by lipid-specific endosomal escape of supercharged branched peptides [J].
Brock, Dakota J. ;
Kustigian, Lauren ;
Jiang, Mengqiu ;
Graham, Kristin ;
Wang, Ting-Yi ;
Erazo-Oliveras, Alfredo ;
Najjar, Kristina ;
Zhang, Junjie ;
Rye, Hays ;
Pellois, Jean-Philippe .
TRAFFIC, 2018, 19 (06) :421-435
[5]   Tat peptide-mediated cellular delivery:: back to basics [J].
Brooks, H ;
Lebleu, B ;
Vivès, E .
ADVANCED DRUG DELIVERY REVIEWS, 2005, 57 (04) :559-577
[6]   Internalization and endosomal degradation of receptor-bound antigens regulate the efficiency of cross presentation by human dendritic cells [J].
Chatterjee, Bithi ;
Smed-Soerensen, Anna ;
Cohn, Lillian ;
Chalouni, Cecile ;
Vandlen, Richard ;
Lee, Byoung-Chul ;
Widger, Jenifer ;
Keler, Tibor ;
Delamarre, Lelia ;
Mellman, Ira .
BLOOD, 2012, 120 (10) :2011-2020
[7]   Cathepsin B launches an apoptotic exit effort upon cell death-associated disruption of lysosomes [J].
de Castro, M. A. G. ;
Bunt, G. ;
Wouters, F. S. .
CELL DEATH DISCOVERY, 2016, 2
[8]  
DIMENT S, 1985, J BIOL CHEM, V260, P5311
[9]   A comprehensive model for the cellular uptake of cationic cell-penetrating peptides [J].
Duchardt, Falk ;
Fotin-Mleczek, Mariola ;
Schwarz, Heinz ;
Fischer, Rainer ;
Brock, Roland .
TRAFFIC, 2007, 8 (07) :848-866
[10]   The Late Endosome and Its Lipid BMP Act as Gateways for Efficient Cytosolic Access of the Delivery Agent dfTAT and Its Macromolecular Cargos [J].
Erazo-Oliveras, Alfredo ;
Najjar, Kristina ;
Dat Truong ;
Wang, Ting-Yi ;
Brock, Dakota J. ;
Prater, Austin R. ;
Pellois, Jean-Philippe .
CELL CHEMICAL BIOLOGY, 2016, 23 (05) :598-607