scholarly journals Oligoalanine helical callipers for cell penetration

2018 ◽  
Vol 54 (50) ◽  
pp. 6919-6922 ◽  
Author(s):  
Marta Pazo ◽  
Marisa Juanes ◽  
Irene Lostalé-Seijo ◽  
Javier Montenegro
Keyword(s):  
Amino Acids ◽  
Rational Design ◽  
Chemical Space ◽  
Cell Penetrating Peptides ◽  
Short Peptides ◽  
Cell Penetration ◽  
Basic Amino Acids ◽  
Cell Penetrating ◽  
Natural Amino Acids

Even for short peptides that are enriched in basic amino acids, the large chemical space that can be spanned by combinations of natural amino acids hinders the rational design of cell penetrating peptides.

scholarly journals Cell-Penetrating Peptides: Emerging Tools for mRNA Delivery

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 78
Author(s):  
Hidetomo Yokoo ◽  
Makoto Oba ◽  
Satoshi Uchida
Keyword(s):  
Amino Acids ◽  
Genetic Diseases ◽  
Cell Penetrating Peptides ◽  
Delivery Systems ◽  
Endosomal Escape ◽  
Messenger Rnas ◽  
Distinctive Features ◽  
Cell Penetrating ◽  
Preventive Vaccination ◽  
Natural Amino Acids

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.

A Novel Amino Acid Sequence-based Computational Approach to Predicting Cell-penetrating Peptides

2019 ◽  
Vol 15 (3) ◽  
pp. 206-211 ◽  
Author(s):  
Jihui Tang ◽  
Jie Ning ◽  
Xiaoyan Liu ◽  
Baoming Wu ◽  
Rongfeng Hu
Keyword(s):  
Machine Learning ◽  
Amino Acid ◽  
Amino Acid Position ◽  
Cell Penetrating Peptides ◽  
Support Vector ◽  
Cell Penetration ◽  
Drug Candidates ◽  
Machine Learning Model ◽  
Cell Penetrating ◽  
Novel Method

<P>Introduction: Machine Learning is a useful tool for the prediction of cell-penetration compounds as drug candidates. </P><P> Materials and Methods: In this study, we developed a novel method for predicting Cell-Penetrating Peptides (CPPs) membrane penetrating capability. For this, we used orthogonal encoding to encode amino acid and each amino acid position as one variable. Then a software of IBM spss modeler and a dataset including 533 CPPs, were used for model screening. </P><P> Results: The results indicated that the machine learning model of Support Vector Machine (SVM) was suitable for predicting membrane penetrating capability. For improvement, the three CPPs with the most longer lengths were used to predict CPPs. The penetration capability can be predicted with an accuracy of close to 95%. </P><P> Conclusion: All the results indicated that by using amino acid position as a variable can be a perspective method for predicting CPPs membrane penetrating capability.</P>

Development of helix-stabilized cell-penetrating peptides containing cationic α,α-disubstituted amino acids as helical promoters

2017 ◽  
Vol 25 (6) ◽  
pp. 1846-1851 ◽  
Author(s):  
Hiroko Yamashita ◽  
Takashi Misawa ◽  
Makoto Oba ◽  
Masakazu Tanaka ◽  
Mikihiko Naito ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating ◽  
Disubstituted Amino Acids

Stereochemistry as a determining factor for the effect of a cell-penetrating peptide on cellular viability and epithelial integrity

2018 ◽  
Vol 475 (10) ◽  
pp. 1773-1788 ◽  
Author(s):  
Ditlev Birch ◽  
Malene V. Christensen ◽  
Dan Staerk ◽  
Henrik Franzyk ◽  
Hanne Mørck Nielsen
Keyword(s):  
Amino Acids ◽  
Cell Viability ◽  
Mammalian Cells ◽  
Membrane Integrity ◽  
Cell Penetrating Peptides ◽  
Proliferating Cells ◽  
Epithelial Integrity ◽  
Cell Penetrating ◽  
Culture Models ◽  
Well Differentiated

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.

Plasmid DNA delivery by arginine-rich cell-penetrating peptides containing unnatural amino acids

2016 ◽  
Vol 24 (12) ◽  
pp. 2681-2687 ◽  
Author(s):  
Takuma Kato ◽  
Hiroko Yamashita ◽  
Takashi Misawa ◽  
Koyo Nishida ◽  
Masaaki Kurihara ◽  
...  
Keyword(s):  
Amino Acids ◽  
Plasmid Dna ◽  
Unnatural Amino Acids ◽  
Dna Delivery ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating

scholarly journals Rational Design and Synthesis of Novel Dual Protacs for Simultaneous Degradation of EGFR and PARP

2021 ◽  
Author(s):  
Mengzhu Zheng ◽  
Junfeng Huo ◽  
Xiaoxia Gu ◽  
Canrong Wu ◽  
Qingzhe Zhang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Drug Discovery ◽  
Rational Design ◽  
Bispecific Antibodies ◽  
Design And Synthesis ◽  
Synthetic Strategy ◽  
Dual Targeting ◽  
Different Types ◽  
Natural Amino Acids ◽  
Simultaneous Degradation

Inspired by the success of dual targeting drugs, especially bispecific antibodies, we propose to combine the concept of protac and dual targeting to design and synthesize dual protac molecules with the function of degrading two completely different types of targets simultaneously. A library of novel dual targeting protac molecules have been rationally designed and prepared. A convergent synthetic strategy has been utilized to achieve high synthetic efficiency. These dual protac structures are characterized by using trifunctional natural amino acids as star-type core linkers to connect two independent inhibitors and E3 ligands together. In this study, gefitinib, olaparib, and CRBN or VHL E3 ligand were used as substrates to synthesize novel dual protacs. They successfully degraded both EGFR and PARP simultaneously in cancer cells. Being the first successful example of dual protacs, this technique will greatly widen the range of application of the protac method and open up a new field for drug discovery.

Cell Penetrating Mechanism of Bax Inhibiting Peptides.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4298-4298
Author(s):  
Jose A. Gomez ◽  
Tomoyuki Yoshida ◽  
Minh Lam ◽  
Clark W. Distelhorst ◽  
Shigemi Matsuyama
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Fluorescent Dyes ◽  
Cultured Cells ◽  
Cell Penetrating Peptides ◽  
Dependent Manner ◽  
Cell Penetration ◽  
New Members ◽  
Cell Penetrating ◽  
High Degree

Abstract Plasma membrane is known to have a high degree of selectivity for molecular trafficking, and it does not allow the penetration of peptides larger than 3 amino acids. Previously known exceptions of large peptides that penetrate the plasma membrane are the Arginine rich peptides such as human immunodeficiency virus (HIV)-tat peptides. However, the mechanism of cell penetration of these peptides is largely unknown. Bax Inhibiting Peptides (BIP) are penta-peptides derived from the Bax binding domain of Ku70. At present, three types of BIP have been developed. Those are: VPMLK, VPTLK, and VPALR. All of these three BIPs directly bind Bax and inhibit Bax-mediated cell death in cultured cells as well as in animal study. Surprisingly, BIPs are cell permeable and autonomously enter the cytoplasm of the cells within 1 hr. Therefore BIPs are recognized as new members of cell penetration peptides. In this study, we investigated the mechanism of cell penetration of BIPs. DAMI cells (a human megakaryocyte cell line) and HeLa cells were used to investigate the detailed mechanism of cell penetration of BIPs. To detect the cell entry of BIPs, fluorescent dyes (fluorescein or tetramethylrodhamine) were conjugated to the N-terminus of BIPs and the cytoplasmic localization of BIPs was confirmed by confocal microscopy. Cell Penetration activities of BIPs were detected at 1 uM concentration in the culture medium. The significant accumulation of BIPs in the cytoplasm were detected within 1 hour of incubation both at 4 °C and 37 °C, suggesting that ATP-independent mechanism of cell penetration of BIP exists. However, cellular uptake of BIPs reaches plateau at 100 uM at 4 °C, whereas it increases in a dose dependent manner up to 1 mM at 37 °C without any sign of cytotoxicity. These results suggest that there are at least two mechanisms contributing to the cell penetration of BIPs that are, “ATP-independent (4 °C)” and “ATP-dependent (37 °C)” mechanisms. In addition to BIPs, we generated a series of mutated BIPs that do not bind Bax but retain cell-penetrating activities. We performed competition assay using fluorescence dye-labeled and non-labeled BIP (and the mutant BIPs), and the preliminary results suggest that there is a specific receptor for each peptide for its delivery into the cells. Our data also indicates that BIPs can deliver a cargo molecule (e.g. fluorescent dye) with at least the same molecular weight. Unlike other cell penetrating peptides, BIP has minimum toxicity due to its nature to inhibit Bax-mediated cell death. Along with the new data showing that BIP protects cells from pathological damages in cell culture and animal model, we will discuss the potential application of BIPs as a new type of drug delivery tool.

scholarly journals Designed cell penetrating peptide dendrimers efficiently internalize cargo into cells

2014 ◽  
Vol 50 (55) ◽  
pp. 7254-7257 ◽  
Author(s):  
Gabriela A. Eggimann ◽  
Emilyne Blattes ◽  
Stefanie Buschor ◽  
Rasomoy Biswas ◽  
Stephan M. Kammer ◽  
...  
Keyword(s):  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
Cell Penetration ◽  
Lower Toxicity ◽  
Serum Stability ◽  
Peptide Dendrimers ◽  
Cell Penetrating ◽  
Linear Cell

Redesigning linear cell penetrating peptides (CPPs) into a multi-branched topology with short dipeptide branches gave cell penetrating peptide dendrimers (CPPDs) with higher cell penetration, lower toxicity and hemolysis and higher serum stability than linear CPPs.

Enhanced Cell Penetration of Acid-Degradable Particles Functionalized with Cell-Penetrating Peptides

2008 ◽  
Vol 19 (4) ◽  
pp. 876-881 ◽  
Author(s):  
Jessica L. Cohen ◽  
Adah Almutairi ◽  
Joel A. Cohen ◽  
Matt Bernstein ◽  
Steven L. Brody ◽  
...  
Keyword(s):  
Cell Penetrating Peptides ◽  
Cell Penetration ◽  
Cell Penetrating
Sign in / Sign up

Export Citation Format

Share Document