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 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 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 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 Using molecular dynamics simulations to prioritize and understand AI-generated cell penetrating peptides

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Duy Phuoc Tran ◽  
Seiichi Tada ◽  
Akiko Yumoto ◽  
Akio Kitao ◽  
Yoshihiro Ito ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
De Novo ◽  
Homology Modelling ◽  
Md Simulations ◽  
Cell Penetrating Peptides ◽  
Generative Models ◽  
Cell Penetrating ◽  
Wet Lab ◽  
Dynamics Simulations ◽  
De Novo Peptide

AbstractCell-penetrating peptides have important therapeutic applications in drug delivery, but the variety of known cell-penetrating peptides is still limited. With a promise to accelerate peptide development, artificial intelligence (AI) techniques including deep generative models are currently in spotlight. Scientists, however, are often overwhelmed by an excessive number of unannotated sequences generated by AI and find it difficult to obtain insights to prioritize them for experimental validation. To avoid this pitfall, we leverage molecular dynamics (MD) simulations to obtain mechanistic information to prioritize and understand AI-generated peptides. A mechanistic score of permeability is computed from five steered MD simulations starting from different initial structures predicted by homology modelling. To compensate for variability of predicted structures, the score is computed with sample variance penalization so that a peptide with consistent behaviour is highly evaluated. Our computational pipeline involving deep learning, homology modelling, MD simulations and synthesizability assessment generated 24 novel peptide sequences. The top-scoring peptide showed a consistent pattern of conformational change in all simulations regardless of initial structures. As a result of wet-lab-experiments, our peptide showed better permeability and weaker toxicity in comparison to a clinically used peptide, TAT. Our result demonstrates how MD simulations can support de novo peptide design by providing mechanistic information supplementing statistical inference.

Self-Activation in De Novo Designed Mimics of Cell-Penetrating Peptides

2011 ◽  
Vol 123 (27) ◽  
pp. 6271-6274 ◽  
Author(s):  
Abhigyan Som ◽  
A. Ozgul Tezgel ◽  
Gregory J. Gabriel ◽  
Gregory N. Tew
Keyword(s):  
De Novo ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating

Self-Activation in De Novo Designed Mimics of Cell-Penetrating Peptides

2011 ◽  
Vol 50 (27) ◽  
pp. 6147-6150 ◽  
Author(s):  
Abhigyan Som ◽  
A. Ozgul Tezgel ◽  
Gregory J. Gabriel ◽  
Gregory N. Tew
Keyword(s):  
De Novo ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating

The delivery of PEBBLE nanosensors to measure the intracellular environment

2007 ◽  
Vol 35 (3) ◽  
pp. 538-543 ◽  
Author(s):  
A. Webster ◽  
P. Coupland ◽  
F.D. Houghton ◽  
H.J. Leese ◽  
J.W. Aylott
Keyword(s):  
Surface Functionalization ◽  
Cell Types ◽  
Cell Penetrating Peptides ◽  
Cytochalasin D ◽  
Gene Gun ◽  
Intracellular Environment ◽  
Cellular Environment ◽  
Cell Penetrating

Cellular introduction of PEBBLEs (photonic explorers for bioanalysis with biologically localized embedding) has been investigated by a wide variety of methods in a range of cell types. These methods include surface functionalization with CPPs (cell-penetrating peptides), pinocytosis, commercial lipid transfection agents, cytochalasin D, picoinjection, and Gene gun bombardment. This paper will overview several of the most popular methods used for the introduction of PEBBLE nanosensors to the cellular environment and discuss the efficacy of the techniques.

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.

scholarly journals Bio-Membrane Internalization Mechanisms of Arginine-Rich Cell-Penetrating Peptides in Various Species

Membranes ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 88
Author(s):  
Betty Revon Liu ◽  
Shiow-Her Chiou ◽  
Yue-Wern Huang ◽  
Han-Jung Lee
Keyword(s):  
Plasma Membranes ◽  
Cell Penetrating Peptides ◽  
Cellular Delivery ◽  
Drug Molecules ◽  
Cargo Delivery ◽  
Cell Penetrating ◽  
Key Factor ◽  
Potential Applications ◽  
Primary Key ◽  
Potent Drug

Recently, membrane-active peptides or proteins that include antimicrobial peptides (AMPs), cytolytic proteins, and cell-penetrating peptides (CPPs) have attracted attention due to their potential applications in the biomedical field. Among them, CPPs have been regarded as a potent drug/molecules delivery system. Various cargoes, such as DNAs, RNAs, bioactive proteins/peptides, nanoparticles and drugs, can be carried by CPPs and delivered into cells in either covalent or noncovalent manners. Here, we focused on four arginine-rich CPPs and reviewed the mechanisms that these CPPs used for intracellular uptake across cellular plasma membranes. The varying transduction efficiencies of them alone or with cargoes were discussed, and the membrane permeability was also expounded for CPP/cargoes delivery in various species. Direct membrane translocation (penetration) and endocytosis are two principal mechanisms for arginine-rich CPPs mediated cargo delivery. Furthermore, the amino acid sequence is the primary key factor that determines the cellular internalization mechanism. Importantly, the non-cytotoxic nature and the wide applicability make CPPs a trending tool for cellular delivery.

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