Intelligent substance delivery into cells using cell-penetrating peptides

Tashima, Toshihiko

doi:10.1016/j.bmcl.2016.11.083

Cited by 59 publications

(48 citation statements)

References 72 publications

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“…Thus, endocytosis seems to be the main entry pathway for [ 64 Cu]Cu-sC18(NIA) 2 . However, as already discussed, CPP-mediated transport might happen through different endocytosis routes, like macropinocytosis, caveolaedependent, or clathrin-dependent pathways, or in the trans-Golgi network [36]. Which pathway exactly is used in this case cannot be concluded from the present data.…”

Section: Cellular Uptake Studies Of Radiolabeled Peptidesmentioning

confidence: 55%

Biological characterization of novel nitroimidazole‐peptide conjugates in vitro and in vivo

Bergmann

Splith

Pietzsch

et al. 2017

Journal of Peptide Science

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Recently, we reported on the design of a multimodal peptide conjugate useful as delivery platform for targeting hypoxic cells. A nitroimidazole (2-(2-nitroimidazol-1-yl)acetic acid, NIA) moiety, which is selectively entrapped in hypoxic cells, was coupled to a cell-penetrating peptide serving as the transporter. Furthermore, attachment of a bifunctional linker allowed the introduction of a diagnostic or therapeutic radiometal. However, although selective tumor accumulation could be detected in vivo, a fast renal clearance of the compound was observed. The present study aims to improve the system by using the more proteolytically stable all-d version of the peptide carrier (DsC18), by attaching two NIA moieties instead of one (DsC18(NIA) ) to enhance the tumor uptake, and by incorporating the bifunctional chelator NODAGA instead of DOTA (NODAGA-DsC18(NIA) ) to optimize labeling chemistry. First, we characterized in vitro the novel all-d peptide compared with its parent l-version. Then, in order to investigate and compare the pharmacological profiles of the peptides, these were radiolabeled with Cu and Ga , and the biodistribution and kinetics were evaluated in vivo. Our results show the versatility of the d-peptide as cell-penetrating peptide and transporter. However, attaching two NIA groups modified the system in such a way that no selective tumor uptake could be observed compared with the peptide without NIA moieties. Still, this work highlights new pharmacokinetic data on the biodistribution of such compounds in vivo. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

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Section: Cellular Uptake Studies Of Radiolabeled Peptidesmentioning

confidence: 55%

Biological characterization of novel nitroimidazole‐peptide conjugates in vitro and in vivo

Bergmann

Splith

Pietzsch

et al. 2017

Journal of Peptide Science

View full text Add to dashboard Cite

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“…Cell-penetrating peptides (CPPs) such as TAT, are promising therapeutic delivery systems that have been used for the treatment of several diseases [90]. Their versatility is based on the fact that CPPs are applicable to all cell types with high transduction efficiency under controlled administration [91]. CPPs have been used for delivery of large cargos including biomolecules (such as nucleic acids and large proteins with low transmembrane permeability) [91–94] and drugs [95, 96].…”

Section: Transcription Activator-like Effector Nucleases (Talens)mentioning

confidence: 99%

“…Their versatility is based on the fact that CPPs are applicable to all cell types with high transduction efficiency under controlled administration [91]. CPPs have been used for delivery of large cargos including biomolecules (such as nucleic acids and large proteins with low transmembrane permeability) [91–94] and drugs [95, 96]. A dose-dependent TAT-TALEN activity was observed under hypothermic conditions with disruption efficiency of 3 and 5% with HeLa and hiPSCs respectively.…”

Section: Transcription Activator-like Effector Nucleases (Talens)mentioning

confidence: 99%

The therapeutic landscape of HIV-1 via genome editing

2017

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Current treatment for HIV-1 largely relies on chemotherapy through the administration of antiretroviral drugs. While the search for anti-HIV-1 vaccine remain elusive, the use of highly active antiretroviral therapies (HAART) have been far-reaching and has changed HIV-1 into a manageable chronic infection. There is compelling evidence, including several side-effects of ARTs, suggesting that eradication of HIV-1 cannot depend solely on antiretrovirals. Gene therapy, an expanding treatment strategy, using RNA interference (RNAi) and programmable nucleases such as meganuclease, zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins (CRISPR–Cas9) are transforming the therapeutic landscape of HIV-1. TALENS and ZFNS are structurally similar modular systems, which consist of a FokI endonuclease fused to custom-designed effector proteins but have been largely limited, particularly ZFNs, due to their complexity and cost of protein engineering. However, the newly developed CRISPR–Cas9 system, consists of a single guide RNA (sgRNA), which directs a Cas9 endonuclease to complementary target sites, and serves as a superior alternative to the previous protein-based systems. The techniques have been successfully applied to the development of better HIV-1 models, generation of protective mutations in endogenous/host cells, disruption of HIV-1 genomes and even reactivating latent viruses for better detection and clearance by host immune response. Here, we focus on gene editing-based HIV-1 treatment and research in addition to providing perspectives for refining these techniques.

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“…Chemical conjugateso fN ATsw ith bioactive peptidesh ave advantageous pharmacological properties, cellular uptake, and therapeutic efficacy. [18] By using advanced methodsf or peptide synthesis, pure, biologically active peptides can now be prepared. In particular,s olid-phase automated peptides ynthesis (SPPS), [19] artificial cellular factories, and advanced purification strategies find application in the field of synthetic peptides.…”

Section: Synthetic Peptides and Their Analogues For Natbioconjugationmentioning

confidence: 99%

Synthetic Nucleic Acid Analogues in Gene Therapy: An Update for Peptide–Oligonucleotide Conjugates

2017

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The main objective of this work is to provide an update on synthetic nucleic acid analogues and nanoassemblies as tools in gene therapy. In particular, the synthesis and properties of peptide-oligonucleotide conjugates (POCs), which have high potential in research and as therapeutics, are described in detail. The exploration of POCs has already led to fruitful results in the treatment of neurological diseases, lung disorders, cancer, leukemia, viral, and bacterial infections. However, delivery and in vivo stability are the major barriers to the clinical application of POCs and other analogues that still have to be overcome. This review summarizes recent achievements in the delivery and in vivo administration of synthetic nucleic acid analogues, focusing on POCs, and compares their efficiency.

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Intelligent substance delivery into cells using cell-penetrating peptides

Cited by 59 publications

References 72 publications

Biological characterization of novel nitroimidazole‐peptide conjugates in vitro and in vivo

Biological characterization of novel nitroimidazole‐peptide conjugates in vitro and in vivo

The therapeutic landscape of HIV-1 via genome editing

Synthetic Nucleic Acid Analogues in Gene Therapy: An Update for Peptide–Oligonucleotide Conjugates

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