Classes and Applications of Cell-Penetrating Peptides

Langel, Ülo

doi:10.1007/978-981-13-8747-0_2

Cited by 21 publications

(23 citation statements)

References 341 publications

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“…It was clear that, to obtain nuclear activity with LNA/OMe ONs required for inhibition of Tat-dependent trans -activation, it was necessary to formulate the steric blocking ON with a cationic lipid delivery agent. As a more practical alternative to avoid the use of complex formulation strategies and which might be more appropriate for therapeutic development, certain covalently attached CPPs [23] were investigated to deliver steric blocking LNA/OMe ONs into the nucleus of cells to inhibit Tat-dependent trans -activation [24]. Although uptake into the cell nucleus had been observed with fluorescent ON-CPP conjugates previously, reviewed in reference [25], many of such results were likely to have been compromised by the use of strong cell fixatives that altered the cell distribution of CPPs during such use [26].…”

Section: Cell Delivery By Conjugates Of Ons With Cppsmentioning

confidence: 99%

Cell-Penetrating Peptide Conjugates of Steric Blocking Oligonucleotides as Therapeutics for Neuromuscular Diseases from a Historical Perspective to Current Prospects of Treatment

Gait

Arzumanov

McClorey

et al. 2019

Nucleic Acid Therapeutics

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The review starts with a historical perspective of the achievements of the Gait group in synthesis of oligo-nucleotides (ONs) and their peptide conjugates toward the award of the 2017 Oligonucleotide Therapeutic Society Lifetime Achievement Award. This acts as a prelude to the rewarding collaborative studies in the Gait and Wood research groups aimed toward the enhanced delivery of charge neutral ON drugs and the development of a series of Arg-rich cell-penetrating peptides called Pip (peptide nucleic acid/phosphorodiamidate morpholino oligonucleotide [PNA/PMO] internalization peptides) as conjugates of such ONs. In this review we concentrate on these developments toward the treatment of the neuromuscular diseases Duchenne muscular dystrophy and spinal muscular atrophy toward a platform technology for the enhancement of cellular and in vivo delivery suitable for widespread use as neuromuscular and neurodegenerative ON drugs.

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Section: Cell Delivery By Conjugates Of Ons With Cppsmentioning

confidence: 99%

Cell-Penetrating Peptide Conjugates of Steric Blocking Oligonucleotides as Therapeutics for Neuromuscular Diseases from a Historical Perspective to Current Prospects of Treatment

Gait

Arzumanov

McClorey

et al. 2019

Nucleic Acid Therapeutics

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“…Cell penetrating peptides (CPP) [ 4 , 5 , 6 ] are potential carriers for DDS. They consist of 5–30 amino acid-long peptides which are capable of transporting the cargo molecule into the intracellular space in the absence of a cognate transporter.…”

Section: Introductionmentioning

confidence: 99%

Chiral Cyclobutane-Containing Cell-Penetrating Peptides as Selective Vectors for Anti-Leishmania Drug Delivery Systems

Illa

Olivares

Gaztelumendi

et al. 2020

IJMS

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Two series of new hybrid γ/γ-peptides, γ-CC and γ-CT, formed by (1S,2R)-3-amino-2,2,dimethylcyclobutane-1-carboxylic acid joined in alternation to a Nα-functionalized cis- or trans-γ-amino-l-proline derivative, respectively, have been synthesized and evaluated as cell penetrating peptides (CPP) and as selective vectors for anti-Leishmania drug delivery systems (DDS). They lacked cytotoxicity on the tumoral human cell line HeLa with a moderate cell-uptake on these cells. In contrast, both γ-CC and γ-CT tetradecamers were microbicidal on the protozoan parasite Leishmania beyond 25 μM, with significant intracellular accumulation. They were conjugated to fluorescent doxorubicin (Dox) as a standard drug showing toxicity beyond 1 μM, while free Dox was not toxic. Intracellular accumulation was 2.5 higher than with Dox-TAT conjugate (TAT = transactivator of transcription, taken as a standard CPP). The conformational structure of the conjugates was approached both by circular dichroism spectroscopy and molecular dynamics simulations. Altogether, computational calculations predict that the drug-γ-peptide conjugates adopt conformations that bury the Dox moiety into a cavity of the folded peptide, while the positively charged guanidinium groups face the solvent. The favorable charge/hydrophobicity balance in these CPP improves the solubility of Dox in aqueous media, as well as translocation across cell membranes, making them promising candidates for DDS.

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“…Mapegin (MAPA) design started from the MAP sequence for the cell-penetrating peptide KLALKLALKALKAALKLA [ 70 ]. There is some confusion in the literature about the primary structure of the MAP CPP [ 71 ].…”

Section: Resultsmentioning

confidence: 99%

The Spectrum of Design Solutions for Improving the Activity-Selectivity Product of Peptide Antibiotics against Multidrug-Resistant Bacteria and Prostate Cancer PC-3 Cells

et al. 2020

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The link between the antimicrobial and anticancer activity of peptides has long been studied, and the number of peptides identified with both activities has recently increased considerably. In this work, we hypothesized that designed peptides with a wide spectrum of selective antimicrobial activity will also have anticancer activity, and tested this hypothesis with newly designed peptides. The spectrum of peptides, used as partial or full design templates, ranged from cell-penetrating peptides and putative bacteriocin to those from the simplest animals (placozoans) and the Chordata phylum (anurans). We applied custom computational tools to predict amino acid substitutions, conferring the increased product of bacteriostatic activity and selectivity. Experiments confirmed that better overall performance was achieved with respect to that of initial templates. Nine of our synthesized helical peptides had excellent bactericidal activity against both standard and multidrug-resistant bacteria. These peptides were then compared to a known anticancer peptide polybia-MP1, for their ability to kill prostate cancer cells and dermal primary fibroblasts. The therapeutic index was higher for seven of our peptides, and anticancer activity stronger for all of them. In conclusion, the peptides that we designed for selective antimicrobial activity also have promising potential for anticancer applications.

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Classes and Applications of Cell-Penetrating Peptides

Cited by 21 publications

References 341 publications

Cell-Penetrating Peptide Conjugates of Steric Blocking Oligonucleotides as Therapeutics for Neuromuscular Diseases from a Historical Perspective to Current Prospects of Treatment

Cell-Penetrating Peptide Conjugates of Steric Blocking Oligonucleotides as Therapeutics for Neuromuscular Diseases from a Historical Perspective to Current Prospects of Treatment

Chiral Cyclobutane-Containing Cell-Penetrating Peptides as Selective Vectors for Anti-Leishmania Drug Delivery Systems

The Spectrum of Design Solutions for Improving the Activity-Selectivity Product of Peptide Antibiotics against Multidrug-Resistant Bacteria and Prostate Cancer PC-3 Cells

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