scholarly journals Selective Moonlighting Cell-Penetrating Peptides

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1119
Author(s):  
Rafael Morán-Torres ◽  
David A. Castillo González ◽  
Maria Luisa Durán-Pastén ◽  
Beatriz Aguilar-Maldonado ◽  
Susana Castro-Obregón ◽  
...  
Keyword(s):  
Target Recognition ◽  
Active Form ◽  
Cell Types ◽  
Cell Penetrating Peptides ◽  
Machine Learning Methods ◽  
Cell Penetrating ◽  
Cell Target ◽  
The Cost ◽  
Multifunctional Peptides ◽  
Different Cell Types

Cell penetrating peptides (CPPs) are molecules capable of passing through biological membranes. This capacity has been used to deliver impermeable molecules into cells, such as drugs and DNA probes, among others. However, the internalization of these peptides lacks specificity: CPPs internalize indistinctly on different cell types. Two major approaches have been described to address this problem: I) targeting, in which a receptor-recognizing sequence is added to a CPP, and ii) activation, where a non-active form of the CPP is activated once it interacts with cell target components. These strategies result in multifunctional peptides (i.e., penetrate and target recognition) that increase the CPP’s length, the cost of synthesis and the likelihood to be degraded or become antigenic. In this work we describe the use of machine-learning methods to design short selective CPP; the reduction in size is accomplished by embedding two or more activities within a single CPP domain, hence we referred to these as moonlighting CPPs. We provide experimental evidence that these designed moonlighting peptides penetrate selectively in targeted cells and discuss areas of opportunity to improve in the design of these peptides.

scholarly journals Internalization mechanisms of cell-penetrating peptides

2020 ◽  
Vol 11 ◽  
pp. 101-123 ◽  
Author(s):  
Ivana Ruseska ◽  
Andreas Zimmer
Keyword(s):  
Cellular Uptake ◽  
Cell Types ◽  
Cell Penetrating Peptides ◽  
Uptake Mechanism ◽  
Black And White ◽  
Cell Penetrating ◽  
Basic Peptides ◽  
Different Cell Types ◽  
Immense Potential

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.

scholarly journals Cell penetrating peptides can exert biological activity: a review

2010 ◽  
Vol 1 (2) ◽  
pp. 109-116 ◽  
Author(s):  
Jamie Brugnano ◽  
Brian C. Ward ◽  
Alyssa Panitch
Keyword(s):  
Gene Expression ◽  
Biological Activity ◽  
Cell Membrane ◽  
Recent Literature ◽  
Cell Types ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating ◽  
Different Cell Types ◽  
Traditional Understanding

AbstractCell penetrating peptides (CPPs) have been successful in delivering cargo into many different cell types and are an important alternative to other methods of permeation that might damage the integrity of the cell membrane. The traditional view of CPPs is that they are inert molecules that can be successfully used to deliver many cargos intracellularly. The goal of this review is to challenge this traditional understanding of CPPs. Recent literature has demonstrated that CPPs themselves can convey biological activity, including the alteration of gene expression and inhibition of protein kinases and proteolytic activity. Further characterization of CPPs is required to determine the extent of this activity. Research into the use of CPPs for intracellular delivery should continue with investigators being aware of these recent results.

scholarly journals Statin-boosted cellular uptake of penetratin due to reduced membrane dipole potential

2020 ◽  
Author(s):  
Gyula Batta ◽  
Levente Kárpáti ◽  
Gabriela Fulaneto Henrique ◽  
Szabolcs Tarapcsák ◽  
Tamás Kovács ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Cell Types ◽  
Cell Penetrating Peptides ◽  
Dipole Potential ◽  
Membrane Dipole Potential ◽  
Cell Penetrating ◽  
Ph Sensitive Dyes ◽  
Coa Reductase ◽  
Endocytic Compartments ◽  
Different Cell Types

AbstractSince cell penetrating peptides are promising tools for delivery of cargo into cells, factors limiting or facilitating their cellular uptake are intensely studied. Using labeling with pH-insensitive and pH-sensitive dyes we report that escape of penetratin from acidic endo-lysosomal compartments is retarded compared to its cellular uptake. The membrane dipole potential, known to alter transmembrane transport of charged molecules, is shown to be negatively correlated with the concentration of penetratin in the cytoplasmic compartment. Treatment of cells with therapeutically relevant concentrations of atorvastatin, an inhibitor of HMG-CoA reductase and cholesterol synthesis, significantly increased the release of penetratin from acidic endocytic compartments in two different cell types. This effect of atorvastatin correlated with its ability to decrease the membrane dipole potential. These results highlight the importance of the dipole potential in regulating cellular uptake of cell penetrating peptides and suggest a clinically relevant way of boosting this process.

Processing and Characterization of Recombinant von Willebrand Factor Expressed in Different Cell Types Using a Vaccinia Virus Vector

1992 ◽  
Vol 67 (01) ◽  
pp. 154-160 ◽  
Author(s):  
P Meulien ◽  
M Nishino ◽  
C Mazurier ◽  
K Dott ◽  
G Piétu ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Von Willebrand Factor ◽  
Human Fibroblasts ◽  
Active Form ◽  
Cell Types ◽  
Biologically Active ◽  
L Cells ◽  
Von Willebrand ◽  
Different Cell Types ◽  
Willebrand Factor

SummaryThe cloning of the cDNA encoding von Willebrand factor (vWF) has revealed that it is synthesized as a large precursor (pre-pro-vWF) molecule and it is now clear that the prosequence or vWAgll is responsible for the intracellular multimerization of vWF. We have cloned the complete vWF cDNA and expressed it using a recombinant vaccinia virus as vector. We have characterized the structure and function of the recombinant vWF (rvWF) secreted from five different cell types: baby hamster kidney (BHK), Chinese hamster ovary (CHO), human fibroblasts (143B), mouse fibroblasts (L) and primary embryonic chicken cells. Forty-eight hours after infection, the quantity of vWF antigen found in the cell supernatant varied from 3 to 12 U/dl depending on the cell type. By SDS-agarose gel electrophoresis, the percentage of high molecular weight forms of vWF varied from 39 to 49% relative to normal plasma for BHK, CHO, 143B and chicken cells but was less than 10% for L cells. In all cell types, the two anodic subbands of each multimer were missing. The two cathodic subbands were easily detected only in BHK and L cells. By SDS-PAGE of reduced samples, pro-vWF was present in similar quantity to the fully processed vWF subunit in L cells, present in moderate amounts in BHK and CHO and in very low amounts in 143B and chicken cells. rvWF from all cells bound to collagen and to platelets in the presence of ristocetin, the latter showing a high correlation between binding efficiency and degree of multimerization. rvWF from all cells was also shown to bind to purified FVIII and in this case binding appeared to be independent of the degree of multimerization. We conclude that whereas vWF is naturally synthesized only by endothelial cells and megakaryocytes, it can be expressed in a biologically active form from various other cell types.

scholarly journals The Utilization of Cell-Penetrating Peptides in the Intracellular Delivery of Viral Nanoparticles

Materials ◽  
2019 ◽  
Vol 12 (17) ◽  
pp. 2671 ◽  
Author(s):  
Jana Váňová ◽  
Alžběta Hejtmánková ◽  
Marie Hubálek Kalbáčová ◽  
Hana Španielová
Keyword(s):  
Genetic Material ◽  
Cell Types ◽  
Cell Penetrating Peptides ◽  
Target Cells ◽  
Current State ◽  
Cargo Delivery ◽  
Viral Particles ◽  
Cell Penetrating ◽  
Viral Nanoparticles ◽  
Immunogenic Properties

Viral particles (VPs) have evolved so as to efficiently enter target cells and to deliver their genetic material. The current state of knowledge allows us to use VPs in the field of biomedicine as nanoparticles that are safe, easy to manipulate, inherently biocompatible, biodegradable, and capable of transporting various cargoes into specific cells. Despite the fact that these virus-based nanoparticles constitute the most common vectors used in clinical practice, the need remains for further improvement in this area. The aim of this review is to discuss the potential for enhancing the efficiency and versatility of VPs via their functionalization with cell-penetrating peptides (CPPs), short peptides that are able to translocate across cellular membranes and to transport various substances with them. The review provides and describes various examples of and means of exploitation of CPPs in order to enhance the delivery of VPs into permissive cells and/or to allow them to enter a broad range of cell types. Moreover, it is possible that CPPs are capable of changing the immunogenic properties of VPs, which could lead to an improvement in their clinical application. The review also discusses strategies aimed at the modification of VPs by CPPs so as to create a useful cargo delivery tool.

scholarly journals Cell-Penetrating Peptides Derived from Animal Venoms and Toxins

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 147
Author(s):  
Gandhi Rádis-Baptista
Keyword(s):  
Plasma Membranes ◽  
Cytoplasmic Membrane ◽  
De Novo ◽  
Cell Types ◽  
Cell Penetrating Peptides ◽  
Cumulative Number ◽  
Cell Cytoplasm ◽  
Cell Penetrating ◽  
Animal Venoms ◽  
Pharmaceutical Biotechnology

Cell-penetrating peptides (CPPs) comprise a class of short polypeptides that possess the ability to selectively interact with the cytoplasmic membrane of certain cell types, translocate across plasma membranes and accumulate in the cell cytoplasm, organelles (e.g., the nucleus and mitochondria) and other subcellular compartments. CPPs are either of natural origin or de novo designed and synthesized from segments and patches of larger proteins or designed by algorithms. With such intrinsic properties, along with membrane permeation, translocation and cellular uptake properties, CPPs can intracellularly convey diverse substances and nanomaterials, such as hydrophilic organic compounds and drugs, macromolecules (nucleic acids and proteins), nanoparticles (nanocrystals and polyplexes), metals and radionuclides, which can be covalently attached via CPP N- and C-terminals or through preparation of CPP complexes. A cumulative number of studies on animal toxins, primarily isolated from the venom of arthropods and snakes, have revealed the cell-penetrating activities of venom peptides and toxins, which can be harnessed for application in biomedicine and pharmaceutical biotechnology. In this review, I aimed to collate examples of peptides from animal venoms and toxic secretions that possess the ability to penetrate diverse types of cells. These venom CPPs have been chemically or structurally modified to enhance cell selectivity, bioavailability and a range of target applications. Herein, examples are listed and discussed, including cysteine-stabilized and linear, α-helical peptides, with cationic and amphipathic character, from the venom of insects (e.g., melittin, anoplin, mastoparans), arachnids (latarcin, lycosin, chlorotoxin, maurocalcine/imperatoxin homologs and wasabi receptor toxin), fish (pardaxins), amphibian (bombesin) and snakes (crotamine and cathelicidins).

scholarly journals Enhanced cell target specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

2021 ◽  
Author(s):  
Roslyn M Ray ◽  
Anders Højgaard Hansen ◽  
Maria Taskova ◽  
Bernhard Jandl ◽  
Jonas Hansen ◽  
...  
Keyword(s):  
Cost Effective ◽  
Cell Types ◽  
Lipid Nanoparticles ◽  
Cell Penetrating Peptides ◽  
Rna Aptamers ◽  
Target Tissue ◽  
Rna Aptamer ◽  
Cell Specificity ◽  
Cell Target ◽  
Hiv 1

Lipid nanoparticles (LNPs) constitute a facile and scalable approach for delivery of payloads to human cells. LNPs are relatively immunologically inert and can be produced in a cost effective and scalable manner. However, targeting and delivery of LNPs across the blood brain barrier (BBB) has proven challenging. In an effort to target LNPs to particular cell types as well as generating LNPs that can cross the BBB, we developed and assessed two approaches whereby BBB penetrating peptides Tat or T7, and RNA aptamers targeted to gp160 from HIV or CCR5, a HIV-1 co-receptor, were incorporated into LNPs. We report here that a CCR5 selective RNA aptamer acts to facilitate entry through a simplified BBB model and to drive the uptake of LNPs into CCR5 expressing cells, while the gp160 aptamer did not. We further observed that the addition of cell penetrating peptides, Tat, did not increase BBB penetration above the aptamer loaded LNPs alone. Moreover, we find that these targeted LNPs exhibit low immunogenic and low toxic profiles and that targeted LNPs can traverse the BBB to potentially deliver drugs into the target tissue. This approach highlights the usefulness of aptamer loaded LNPs to increase target cell specificity and potentially, deliverability across the BBB.

scholarly journals Coupling the Antimalarial Cell Penetrating Peptide TP10 to Classical Antimalarial Drugs Primaquine and Chloroquine Produces Strongly Hemolytic Conjugates

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4559 ◽  
Author(s):  
Luísa Aguiar ◽  
Arnau Biosca ◽  
Elena Lantero ◽  
Jiri Gut ◽  
Nuno Vale ◽  
...  
Keyword(s):  
Cell Penetrating Peptides ◽  
Antiplasmodial Activity ◽  
Erythrocyte Membranes ◽  
Cell Penetrating Peptide ◽  
Peptide Conjugates ◽  
Drug Conjugates ◽  
Cell Penetrating ◽  
A Cell ◽  
Peptide Drug Conjugates ◽  
The Cost

Recently, we disclosed primaquine cell penetrating peptide conjugates that were more potent than parent primaquine against liver stage Plasmodium parasites and non-toxic to hepatocytes. The same strategy was now applied to the blood-stage antimalarial chloroquine, using a wide set of peptides, including TP10, a cell penetrating peptide with intrinsic antiplasmodial activity. Chloroquine-TP10 conjugates displaying higher antiplasmodial activity than the parent TP10 peptide were identified, at the cost of an increased hemolytic activity, which was further confirmed for their primaquine analogues. Fluorescence microscopy and flow cytometry suggest that these drug-peptide conjugates strongly bind, and likely destroy, erythrocyte membranes. Taken together, the results herein reported put forward that coupling antimalarial aminoquinolines to cell penetrating peptides delivers hemolytic conjugates. Hence, despite their widely reported advantages as carriers for many different types of cargo, from small drugs to biomacromolecules, cell penetrating peptides seem unsuitable for safe intracellular delivery of antimalarial aminoquinolines due to hemolysis issues. This highlights the relevance of paying attention to hemolytic effects of cell penetrating peptide-drug conjugates.

Hunchback is required for the specification of the early sublineage of neuroblast 7-3 in the Drosophila central nervous system

Development ◽  
2002 ◽  
Vol 129 (4) ◽  
pp. 1027-1036 ◽  
Author(s):  
Tanja Novotny ◽  
Regina Eiselt ◽  
Joachim Urban
Keyword(s):  
Cell Fate ◽  
Important Determinant ◽  
Cell Types ◽  
Cell Fate Specification ◽  
Glia Cells ◽  
Fate Specification ◽  
Important Player ◽  
Mother Cells ◽  
The Cost ◽  
Different Cell Types

The Drosophila ventral nerve cord (VNC) derives from neuroblasts (NBs), which mostly divide in a stem cell mode and give rise to defined NB lineages characterized by specific sets of sequentially generated neurons and/or glia cells. To understand how different cell types are generated within a NB lineage, we have focused on the NB7-3 lineage as a model system. This NB gives rise to four individually identifiable neurons and we show that these cells are generated from three different ganglion mother cells (GMCs). The finding that the transcription factor Hunchback (Hb) is expressed in the early sublineage of NB7-3, which consists of the early NB and the first GMC (GMC7-3a) and its progeny (EW1 and GW), prompted us to investigate its possible role in NB7-3 lineage development. Our analysis revealed that loss of hb results in a lack of the normally Hb-positive neurons, while the later-born neurons (designated as EW2 and EW3) are still present. However, overexpression of hb in the whole lineage leads to additional cells with the characteristics of GMC7-3a-derived neurons, at the cost of EW2 and EW3. Thus, hb is an important determinant in specifying early sublineage identity in the NB7-3 lineage. Using Even-skipped (Eve) as a marker, we have additionally shown that hb is also needed for the determination and/or differentiation of several other early-born neurons, indicating that this gene is an important player in sequential cell fate specification within the Drosophila CNS.

The Development of Machine Learning Methods in Cell-Penetrating Peptides Identification: A Brief Review

2019 ◽  
Vol 20 (3) ◽  
pp. 217-223 ◽  
Author(s):  
Huan-Huan Wei ◽  
Wuritu Yang ◽  
Hua Tang ◽  
Hao Lin
Keyword(s):  
Machine Learning ◽  
Computational Methods ◽  
Cell Penetrating Peptides ◽  
Learning Methods ◽  
Machine Learning Methods ◽  
Drug Molecules ◽  
Development Direction ◽  
Cell Penetrating ◽  
Construction Strategies ◽  
Insight Into

Background:Cell-penetrating Peptides (CPPs) are important short peptides that facilitate cellular intake or uptake of various molecules. CPPs can transport drug molecules through the plasma membrane and send these molecules to different cellular organelles. Thus, CPP identification and related mechanisms have been extensively explored. In order to reveal the penetration mechanisms of a large number of CPPs, it is necessary to develop convenient and fast methods for CPPs identification.Methods:Biochemical experiments can provide precise details for accurately identifying CPP, but these methods are expensive and laborious. To overcome these disadvantages, several computational methods have been developed to identify CPPs. We have performed review on the development of machine learning methods in CPP identification. This review provides an insight into CPP identification.Results:We summarized the machine learning-based CPP identification methods and compared the construction strategies of 11 different computational methods. Furthermore, we pointed out the limitations and difficulties in predicting CPPs.Conclusion:In this review, the last studies on CPP identification using machine learning method were reported. We also discussed the future development direction of CPP recognition with computational methods.

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