scholarly journals Cell-Penetrating Peptides Predicted From CASC3, AKIP1, and AHRR Proteins

2021 ◽  
Vol 12 ◽  
Author(s):  
Ly Porosk ◽  
Kaisa Põhako ◽  
Piret Arukuusk ◽  
Ülo Langel
Keyword(s):  
Special Property ◽  
Cell Penetrating Peptides ◽  
Therapeutic Applications ◽  
Protein Protein Interaction ◽  
Cell Internalization ◽  
Cell Penetrating ◽  
Peptide Prediction ◽  
Small Molecule Modulators ◽  
Multifunctional Peptides ◽  
Intracellular Targets

Peptides can be used as research tools and for diagnostic or therapeutic applications. Peptides, alongside small molecules and antibodies, are used and are gaining further interest as protein-protein interaction (PPI) modulators. Peptides have high target specificity and high affinity, but, unlike small molecule modulators, they are not able to cross the cell membranes to reach their intracellular targets. To overcome this limitation, the special property of the cell-penetrating peptides (CPPs) could benefit their cause. CPPs are a class of peptides that can enter the cells and with them also deliver the attached cargoes. Today, with the advancement of in silico prediction tools and the availability of protein databases, designing new and multifunctional peptides that are able to reach intracellular targets and inhibit certain cellular processes in a very specific manner is reachable. Although there are several efficient CPP sequences already known, the discovery of new CPPs is crucial for the development of efficient delivery methods for both biotechnological and therapeutic applications. In this work, we chose 10 human nuclear proteins from which we predicted new potential CPP sequences by using three different CPP predictors: cell-penetrating peptide prediction tool, CellPPD, and SkipCPP-Pred. From each protein, one predicted CPP sequence was synthesized and its internalization into cells was assessed. Out of the tested sequences, three peptides displayed features characteristic to CPPs. These peptides and also the predicted peptide sequences could be used to design and modify new CPPs. In this work, we show that we can use protein sequences as input for generating new peptides with cell internalization properties. Three new CPPs, AHRR8-24, CASC3251-264, and AKIP127-37, can be further used for the delivery of other cargoes or designed into multifunctional peptides with capability of internalizing cells.

scholarly journals β-Lactamase Tools for Establishing Cell Internalization and Cytosolic Delivery of Cell Penetrating Peptides

Biomolecules ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 51 ◽  
Author(s):  
Shane Stone ◽  
Tatjana Heinrich ◽  
Suzy Juraja ◽  
Jiulia Satiaputra ◽  
Clinton Hall ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Cell Penetrating Peptides ◽  
Stable Cell Line ◽  
Intracellular Space ◽  
Biologically Relevant ◽  
Cell Internalization ◽  
Cytosolic Delivery ◽  
Cell Penetrating ◽  
Split Protein

The ability of cell penetrating peptides (CPPs) to deliver biologically relevant cargos into cells is becoming more important as targets in the intracellular space continue to be explored. We have developed two assays based on CPP-dependent, intracellular delivery of TEM-1 β-lactamase enzyme, a functional biological molecule comparable in size to many protein therapeutics. The first assay focuses on the delivery of full-length β-lactamase to evaluate the internalization potential of a CPP sequence. The second assay uses a split-protein system where one component of β-lactamase is constitutively expressed in the cytoplasm of a stable cell line and the other component is delivered by a CPP. The delivery of a split β-lactamase component evaluates the cytosolic delivery capacity of a CPP. We demonstrate that these assays are rapid, flexible and have potential for use with any cell type and CPP sequence. Both assays are validated using canonical and novel CPPs, with limits of detection from <500 nM to 1 µM. Together, the β-lactamase assays provide compatible tools for functional characterization of CPP activity and the delivery of biological cargos into cells.

scholarly journals Molecular partners for interaction and cell internalization of cell-penetrating peptides: how identical are they?

Nanomedicine ◽  
2012 ◽  
Vol 7 (1) ◽  
pp. 133-143 ◽  
Author(s):  
Astrid Walrant ◽  
Chérine Bechara ◽  
Isabel D Alves ◽  
Sandrine Sagan
Keyword(s):  
Cell Penetrating Peptides ◽  
Cell Internalization ◽  
Cell Penetrating

scholarly journals Cell-Penetrating Peptides: a Useful Tool for the Delivery of Various Cargoes Into Cells

2018 ◽  
pp. S267-S279 ◽  
Author(s):  
E. BÖHMOVÁ ◽  
D. MACHOVÁ ◽  
M. PECHAR ◽  
R. POLA ◽  
K. VENCLÍKOVÁ ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Cellular Membrane ◽  
Cell Penetrating Peptides ◽  
Cell Entry ◽  
Biologically Active ◽  
Cell Internalization ◽  
Structural Types ◽  
Cell Penetrating ◽  
History Of ◽  
Preclinical And Clinical Studies

Cell-penetrating compounds are substances that enhance the cellular uptake of various molecular cargoes that do not easily cross the cellular membrane. The majority of cell-penetrating compounds described in the literature are cell-penetrating peptides (CPPs). This review summarizes the various structural types of cell-penetrating compounds, with the main focus on CPPs. The authors present a brief overview of the history of CPPs, discuss the various types of conjugation of CPPs to biologically active cargoes intended for cell internalization, examine the cell-entry mechanisms of CPPs, and report on the applications of CPPs in research and in preclinical and clinical studies.

scholarly journals Decoding the Proteome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) for Cell-Penetrating Peptides Involved in Pathogenesis or Applicable as Drug Delivery Vectors

2020 ◽  
Author(s):  
Shiva Hemmati ◽  
Yasaman Behzadipour ◽  
Mahdi Haddad
Keyword(s):  
Drug Delivery ◽  
Severe Acute Respiratory Syndrome ◽  
Metal Ion ◽  
Cell Penetrating Peptides ◽  
Obligate Intracellular ◽  
Protein Protein Interaction ◽  
Intracellular Parasites ◽  
Cell Penetrating ◽  
Cargo Transportation ◽  
Computational Analyses

Synthetic or natural-derived cell penetrating peptides (CPPs) are vastly investigated as tools for the intracellular delivery of membrane-impermeable molecules. As viruses are obligate intracellular parasites, viral originated CPPs have been considered as suitable shuttling vectors for cargo transportation. A total of 310 CPPs were identified in the proteome of SARS-CoV-2. SCV2-CPPs span the regions involved in replication, protein-nucleotide and protein-protein interaction, protein-metal ion interaction, and stabilization of homo/hetero-oligomers. Computational analyses showed that the most optimal SCV2-CPP candidates as vectors for drug delivery are SCV2-CPP118, SCV2-CPP119, SCV2-CPP122, and SCV2-CPP129 of NSP12. Conclusively, the workflow of this study provides a platform for profound screening of viral proteomes as a rich source of bio-therapeutics or drug delivery carriers. <br>

Cyclic, Cell-Penetrating Peptides Tailor-Made for the Creation of Peptide Libraries with Intrinsic Cell Permeability

2020 ◽  
Author(s):  
Nicolas A. Abrigo ◽  
Kara Dods ◽  
Koushambi Mitra ◽  
Kaylee Newcomb ◽  
Anthony Le ◽  
...  
Keyword(s):  
Cyclic Peptide ◽  
Cell Penetrating Peptides ◽  
Peptide Libraries ◽  
Cell Permeability ◽  
Side Chain ◽  
High Affinity ◽  
Cell Penetrating ◽  
The Creation ◽  
Intracellular Targets ◽  
Macrocyclic Peptide

<p>The discovery of high-affinity peptides to many intracellular targets has become feasible through the development of diverse macrocyclic peptide libraries. But lack of cell permeability is a key feature hampering the use of these peptides as therapeutics. Here, we develop a set of small, cyclic peptide carriers that efficiently carry cargoes into the cytosol. These peptides are cyclized via side-chain alkylation, which makes them ideal for the creation of diverse mRNA or phage-displayed libraries with intrinsic cell permeability.</p>

Cyclic, Cell-Penetrating Peptides Tailor-Made for the Creation of Peptide Libraries with Intrinsic Cell Permeability

2020 ◽  
Author(s):  
Nicolas A. Abrigo ◽  
Kara Dods ◽  
Koushambi Mitra ◽  
Kaylee Newcomb ◽  
Anthony Le ◽  
...  
Keyword(s):  
Cyclic Peptide ◽  
Cell Penetrating Peptides ◽  
Peptide Libraries ◽  
Cell Permeability ◽  
Side Chain ◽  
High Affinity ◽  
Cell Penetrating ◽  
The Creation ◽  
Intracellular Targets ◽  
Macrocyclic Peptide

<p>The discovery of high-affinity peptides to many intracellular targets has become feasible through the development of diverse macrocyclic peptide libraries. But lack of cell permeability is a key feature hampering the use of these peptides as therapeutics. Here, we develop a set of small, cyclic peptide carriers that efficiently carry cargoes into the cytosol. These peptides are cyclized via side-chain alkylation, which makes them ideal for the creation of diverse mRNA or phage-displayed libraries with intrinsic cell permeability.</p>

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 Decoding the Proteome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) for Cell-Penetrating Peptides Involved in Pathogenesis or Applicable as Drug Delivery Vectors

2020 ◽  
Author(s):  
Shiva Hemmati ◽  
Yasaman Behzadipour ◽  
Mahdi Haddad
Keyword(s):  
Drug Delivery ◽  
Severe Acute Respiratory Syndrome ◽  
Metal Ion ◽  
Cell Penetrating Peptides ◽  
Obligate Intracellular ◽  
Protein Protein Interaction ◽  
Intracellular Parasites ◽  
Cell Penetrating ◽  
Cargo Transportation ◽  
Computational Analyses

Synthetic or natural-derived cell penetrating peptides (CPPs) are vastly investigated as tools for the intracellular delivery of membrane-impermeable molecules. As viruses are obligate intracellular parasites, viral originated CPPs have been considered as suitable shuttling vectors for cargo transportation. A total of 310 CPPs were identified in the proteome of SARS-CoV-2. SCV2-CPPs span the regions involved in replication, protein-nucleotide and protein-protein interaction, protein-metal ion interaction, and stabilization of homo/hetero-oligomers. Computational analyses showed that the most optimal SCV2-CPP candidates as vectors for drug delivery are SCV2-CPP118, SCV2-CPP119, SCV2-CPP122, and SCV2-CPP129 of NSP12. Conclusively, the workflow of this study provides a platform for profound screening of viral proteomes as a rich source of bio-therapeutics or drug delivery carriers. <br>

scholarly journals Cell-penetrating peptides: Possible transduction mechanisms and therapeutic applications

2016 ◽  
Vol 4 (5) ◽  
pp. 528-534 ◽  
Author(s):  
ZHENGRONG GUO ◽  
HUANYAN PENG ◽  
JIWEN KANG ◽  
DIANXING SUN
Keyword(s):  
Cell Penetrating Peptides ◽  
Therapeutic Applications ◽  
Cell Penetrating ◽  
Transduction Mechanisms

scholarly journals Intracellular delivery of therapeutic antibodies into specific cells using antibody-peptide fusions

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Julie Gaston ◽  
Nicolas Maestrali ◽  
Guilhem Lalle ◽  
Marie Gagnaire ◽  
Alessandro Masiero ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Cell Penetrating Peptides ◽  
Therapeutic Modality ◽  
Therapeutic Antibodies ◽  
Cell Penetration ◽  
C Terminus ◽  
Macromolecular Drugs ◽  
Cell Penetrating ◽  
Intracellular Compartments ◽  
Intracellular Targets

AbstractBecause of their favorable properties as macromolecular drugs, antibodies are a very successful therapeutic modality for interfering with disease-relevant targets in the extracellular space or at the cell membrane. However, a large number of diseases involve cytosolic targets and designing antibodies able to efficiently reach intracellular compartments would expand the antibody-tractable conditions. Here, we genetically fused cell penetrating peptides (CPPs) at various positions to an antibody targeting cancer cells, evaluated the developability features of the resulting antibody-peptide fusions and the ability of selected constructs to reach the cytosol. We first determined positions in the IgG structure that were permissive to CPP incorporation without destabilizing the antibody. Fusing CPPs to the C-terminus of the light chain and either before or after the hinge had the least effect on antibody developability features. These constructs were further evaluated for cell penetration efficiency. Two out of five tested CPPs significantly enhanced antibody penetration into the cytosol, in particular when fused before or after the hinge. Finally, we demonstrate that specific antibody binding to the cell surface target is necessary for efficient cell penetration of the CPP-antibody fusions. This study provides a solid basis for further exploration of therapeutic antibodies for intracellular targets.

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