scholarly journals Synthesis, cellular uptake and HIV-1 Tat-dependent trans-activation inhibition activity of oligonucleotide analogues disulphide-conjugated to cell-penetrating peptides

2005 ◽  
Vol 33 (1) ◽  
pp. 27-42 ◽  
Author(s):  
J. J. Turner
2007 ◽  
Vol 35 (4) ◽  
pp. 784-787 ◽  
Author(s):  
S. Futaki ◽  
I. Nakase ◽  
A. Tadokoro ◽  
T. Takeuchi ◽  
A.T. Jones

As the versatility and use of CPPs (cell-penetrating peptides) as intracellular delivery vectors have been widely accepted, the cellular uptake mechanisms that enable their efficient internalization have become the subject of much interest. Arginine-rich peptides, including HIV-1 Tatp (transactivator of transcription peptide), are regarded as a representative class of CPPs. Evidence suggests that macropinocytosis plays a crucial role in the cellular uptake of these peptides. We have recently shown that treatment of cells with arginine-rich peptides induces activation of Rac protein leading to F-actin (filamentous actin) organization and macropinocytosis. We have also shown that depletion of membrane-associated proteoglycans results in the failure of this signalling pathway, suggesting that membrane-associated proteoglycans may act as a potential receptor for the induction of macropinocytic uptake of arginine-rich peptides. However, when the macropinocytic pathway is inhibited at a low temperature or by cholesterol depletion, these peptides can be internalized by alternative mechanisms, one of which appears to be direct translocation of the peptides through the plasma membrane. This review summarizes the current theories on both endocytic and non-endocytic aspects of internalization of arginine-rich peptides.


2012 ◽  
Vol 9 (1) ◽  
pp. S94
Author(s):  
Shawn Keogan ◽  
Shendra Passic ◽  
Brian Wigdahl ◽  
Fred Krebs

2010 ◽  
Vol 15 (23-24) ◽  
pp. 1103-1103
Author(s):  
Monerah H. Al-Soraj ◽  
Catherine L. Watkins ◽  
Dries Vercauteren ◽  
Stefaan De Smedt ◽  
Kevin Braeckmans ◽  
...  

2015 ◽  
Vol 27 (155) ◽  
pp. 81-88 ◽  
Author(s):  
Ikuhiko Nakase ◽  
Yoshimasa Kawaguchi ◽  
Motoyoshi Nomizu ◽  
Shiroh Futaki

2019 ◽  
Vol 41 (11) ◽  
pp. 1283-1298 ◽  
Author(s):  
Saba Davoodi ◽  
Azam Bolhassani ◽  
Seyed Mehdi Sadat ◽  
Shiva Irani

RSC Advances ◽  
2021 ◽  
Vol 11 (57) ◽  
pp. 36116-36124
Author(s):  
Omar Paulino da Silva Filho ◽  
Muhanad Ali ◽  
Rike Nabbefeld ◽  
Daniel Primavessy ◽  
Petra H. Bovee-Geurts ◽  
...  

Noncovalent functionalization with acylated cell-penetrating peptides achieves an efficient cellular uptake of PLGA and PEG-PLGA nanoparticles.


2011 ◽  
Vol 2 (1) ◽  
Author(s):  
Gisela Lättig-Tünnemann ◽  
Manuel Prinz ◽  
Daniel Hoffmann ◽  
Joachim Behlke ◽  
Caroline Palm-Apergi ◽  
...  

2020 ◽  
Vol 11 ◽  
pp. 101-123 ◽  
Author(s):  
Ivana Ruseska ◽  
Andreas Zimmer

In today’s modern era of medicine, macromolecular compounds such as proteins, peptides and nucleic acids are dethroning small molecules as leading therapeutics. Given their immense potential, they are highly sought after. However, their application is limited mostly due to their poor in vivo stability, limited cellular uptake and insufficient target specificity. Cell-penetrating peptides (CPPs) represent a major breakthrough for the transport of macromolecules. They have been shown to successfully deliver proteins, peptides, siRNAs and pDNA in different cell types. In general, CPPs are basic peptides with a positive charge at physiological pH. They are able to translocate membranes and gain entry to the cell interior. Nevertheless, the mechanism they use to enter cells still remains an unsolved piece of the puzzle. Endocytosis and direct penetration have been suggested as the two major mechanisms used for internalization, however, it is not all black and white in the nanoworld. Studies have shown that several CPPs are able to induce and shift between different uptake mechanisms depending on their concentration, cargo or the cell line used. This review will focus on the major internalization pathways CPPs exploit, their characteristics and regulation, as well as some of the factors that influence the cellular uptake mechanism.


2007 ◽  
Vol 35 (4) ◽  
pp. 775-779 ◽  
Author(s):  
R. Abes ◽  
A.A. Arzumanov ◽  
H.M. Moulton ◽  
S. Abes ◽  
G.D. Ivanova ◽  
...  

Cationic CPPs (cell-penetrating peptides) have been used largely for intracellular delivery of low-molecular-mass drugs, biomolecules and particles. Most cationic CPPs bind to cell-associated glycosaminoglycans and are internalized by endocytosis, although the detailed mechanisms involved remain controversial. Sequestration and degradation in endocytic vesicles severely limits the efficiency of cytoplasmic and/or nuclear delivery of CPP-conjugated material. Re-routing the splicing machinery by using steric-block ON (oligonucleotide) analogues, such as PNAs (peptide nucleic acids) or PMOs (phosphorodiamidate morpholino oligomers), has consequently been inefficient when ONs are conjugated with standard CPPs such as Tat (transactivator of transcription), R9 (nona-arginine), K8 (octalysine) or penetratin in the absence of endosomolytic agents. New arginine-rich CPPs such as (R-Ahx-R)4 (6-aminohexanoic acid-spaced oligo-arginine) or R6 (hexa-arginine)–penetratin conjugated to PMO or PNA resulted in efficient splicing correction at non-cytotoxic doses in the absence of chloroquine. SAR (structure–activity relationship) analyses are underway to optimize these peptide delivery vectors and to understand their mechanisms of cellular internalization.


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