scholarly journals Molecular dynamics study of the internalization of cell-penetrating peptides containing unnatural amino acids across membranes

2021 ◽  
Author(s):  
Joan Gimenez-Dejoz ◽  
Keiji Numata

Peptide-based delivery systems that deliver target molecules into cells have been gaining traction. These systems need cell-penetrating peptides (CPPs), which have the remarkable ability to penetrate into biological membranes and...

2016 ◽  
Vol 24 (12) ◽  
pp. 2681-2687 ◽  
Author(s):  
Takuma Kato ◽  
Hiroko Yamashita ◽  
Takashi Misawa ◽  
Koyo Nishida ◽  
Masaaki Kurihara ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 78
Author(s):  
Hidetomo Yokoo ◽  
Makoto Oba ◽  
Satoshi Uchida

Messenger RNAs (mRNAs) were previously shown to have great potential for preventive vaccination against infectious diseases and therapeutic applications in the treatment of cancers and genetic diseases. Delivery systems for mRNAs, including lipid- and polymer-based carriers, are being developed for improving mRNA bioavailability. Among these systems, cell-penetrating peptides (CPPs) of 4–40 amino acids have emerged as powerful tools for mRNA delivery, which were originally developed to deliver membrane-impermeable drugs, peptides, proteins, and nucleic acids to cells and tissues. Various functionalities can be integrated into CPPs by tuning the composition and sequence of natural and non-natural amino acids for mRNA delivery. With the employment of CPPs, improved endosomal escape efficiencies, selective targeting of dendritic cells (DCs), modulation of endosomal pathways for efficient antigen presentation by DCs, and effective mRNA delivery to the lungs by dry powder inhalation have been reported; additionally, they have been found to prolong protein expression by intracellular stabilization of mRNA. This review highlights the distinctive features of CPP-based mRNA delivery systems.


2012 ◽  
Vol 3 (1) ◽  
Author(s):  
Eisaku Kondo ◽  
Ken Saito ◽  
Yuichi Tashiro ◽  
Kaeko Kamide ◽  
Shusei Uno ◽  
...  

2017 ◽  
Vol 25 (6) ◽  
pp. 1846-1851 ◽  
Author(s):  
Hiroko Yamashita ◽  
Takashi Misawa ◽  
Makoto Oba ◽  
Masakazu Tanaka ◽  
Mikihiko Naito ◽  
...  

2018 ◽  
Vol 475 (10) ◽  
pp. 1773-1788 ◽  
Author(s):  
Ditlev Birch ◽  
Malene V. Christensen ◽  
Dan Staerk ◽  
Henrik Franzyk ◽  
Hanne Mørck Nielsen

Cell-penetrating peptides (CPPs) comprise efficient peptide-based delivery vectors. Owing to the inherent poor enzymatic stability of peptides, CPPs displaying partial or full replacement of l-amino acids with the corresponding d-amino acids might possess advantages as delivery vectors. Thus, the present study aims to elucidate the membrane- and metabolism-associated effects of l-Penetratin (l-PEN) and its corresponding all-d analog (d-PEN). These effects were investigated when exerted on hepatocellular (HepG2) or intestinal (Caco-2 and IEC-6) cell culture models. The head-to-head comparison of these enantiomeric CPPs included evaluation of their effects on cell viability and morphology, epithelial membrane integrity, and cellular ultrastructure. In all investigated cell models, a rapid decrease in cell viability, pronounced membrane perturbation and an altered ultrastructure were detected upon exposure to d-PEN. At equimolar concentrations, these observations were less pronounced or even absent for cells exposed to l-PEN. Both CPPs remained stable for at least 2 h during exposure to proliferating cells (cultured for 24 h), although d-PEN exhibited a longer half-life when compared with that of l-PEN when exposed to well-differentiated cell monolayers (cultured for 18–20 days). Thus, the stereochemistry of the CPP penetratin significantly influences its effects on cell viability and epithelial integrity when profiled against a panel of mammalian cells.


Nanoscale ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 1949-1958 ◽  
Author(s):  
Xinli Gao ◽  
Song Hong ◽  
Zhiping Liu ◽  
Tongtao Yue ◽  
Jure Dobnikar ◽  
...  

We report the molecular dynamics evidence for the direct translocation of CPPs across the membrane driven by the membrane electrostatic potential.


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