Aib-containing peptide analogs: Cellular uptake and utilization in oligonucleotide delivery

Wada, Shun‐ichi; Urase, Tomoe; Ban, Kenta; Sudani, Aya; Kawai, Yui; Hayashi, Junsuke; Urata, Hidehito

doi:10.1016/j.bmc.2014.10.040

Cited by 15 publications

(11 citation statements)

References 22 publications

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“…45,68,69 In order to effectively overcome these physical barriers, AONs need to be delivered directly into the human eye, either via injections of naked AONs into the vitreous humor or by using a stabilizing vehicle (e.g., recombinant virus, designed nanoparticles, cell penetrating peptides, exosomes, or liposomes). 35,70,71 Once present in the eye, naked AONs have proven to be able to freely diffuse into all cells of the retina to interfere with splicing. 45 When using naked AONs, it will be needed to repeatedly supplement photoreceptor cells with AONs, since effectiveness will be lost over time due to AON degradation or wash out.…”

Section: Discussionmentioning

confidence: 99%

Antisense Oligonucleotide-based Splice Correction for USH2A-associated Retinal Degeneration Caused by a Frequent Deep-intronic Mutation

Slijkerman

Vaché

Dona

et al. 2016

Molecular Therapy - Nucleic Acids

114

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Usher syndrome (USH) is the most common cause of combined deaf-blindness in man. The hearing loss can be partly compensated by providing patients with hearing aids or cochlear implants, but the loss of vision is currently untreatable. In general, mutations in the USH2A gene are the most frequent cause of USH explaining up to 50% of all patients worldwide. The first deep-intronic mutation in the USH2A gene (c.7595-2144A>G) was reported in 2012, leading to the insertion of a pseudoexon (PE40) into the mature USH2A transcript. When translated, this PE40-containing transcript is predicted to result in a truncated non-functional USH2A protein. In this study, we explored the potential of antisense oligonucleotides (AONs) to prevent aberrant splicing of USH2A pre-mRNA as a consequence of the c.7595-2144A>G mutation. Engineered 2'-O-methylphosphorothioate AONs targeting the PE40 splice acceptor site and/or exonic splice enhancer regions displayed significant splice correction potential in both patient derived fibroblasts and a minigene splice assay for USH2A c.7595-2144A>G, whereas a non-binding sense oligonucleotide had no effect on splicing. Altogether, AON-based splice correction could be a promising approach for the development of a future treatment for USH2A-associated retinitis pigmentosa caused by the deep-intronic c.7595-2144A>G mutation.

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Section: Discussionmentioning

confidence: 99%

Antisense Oligonucleotide-based Splice Correction for USH2A-associated Retinal Degeneration Caused by a Frequent Deep-intronic Mutation

Slijkerman

Vaché

Dona

et al. 2016

Molecular Therapy - Nucleic Acids

114

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“…Peptides possessing multiple Aib residues often form helix structures . Myropeptins A 1 , A 2 , and B ( 1 – 3 ) have 11 Aib residues, which suggests that they can form helix structures.…”

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confidence: 99%

Isolation, Structure Elucidation, and Conformational Regulation of Myropeptins, Lipopeptides from the Fungus Myrothecium roridum

et al. 2019

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Myropeptins, novel lipopeptides, were isolated from the culture broth of a fungus Myrothecium roridum F27113. Myropeptin A 1 comprises a linear 20 amino acid−peptide chain and a lauric acid capping the N-terminus. Myropeptin A 1 formed a helix structure and showed biological activities including antifungal and hemolysis. Myropeptin B, a shorter analogue by two amino acid residues, showed neither helicity nor biological activity. These two amino acids at the C-terminus regulate the molecular function of myropeptin A 1 .

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“…The internalization of the mixed micelles into A549 cells was investigated. Numerous studies have revealed that a well-defined conformation peptide chain exhibited a cell penetrating ability [46][47][48]. The mixed micelles in this study could be detected as rapidly entering into cancer cells by flow cytometry, as Figure 4d shows.…”

Section: Discussionmentioning

confidence: 53%

A Novel pH-Tunable Secondary Conformation Containing Mixed Micellar System in Anticancer Treatment

Shih

Jiang

Lin

et al. 2020

Cancers

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In this study, for the first time, we precisely assembled the poly-γ-benzyl-l-glutamate and an amphiphilic copolymer d-α-tocopherol polyethylene glycol succinate into a mixed micellar system for the embedment of the anticancer drug doxorubicin. Importantly, the intracellular drug-releasing behaviors could be controlled by changing the secondary structures of poly-γ-benzyl-l-glutamate via the precise regulation of the buffer’s pH value. Under neutral conditions, the micellar architectures were stabilized by both α-helix secondary structures and the microcrystalline structures. Under acidic conditions (pH 4.0), the interior structures transformed into a coil state with a disordered alignment, inducing the release of the loaded drug. A remarkable cytotoxicity of the Dox-loaded mixed micelles was exhibited toward human lung cancer cells in vitro. The internalizing capability into the cancer cells, as well as the intracellular drug-releasing behaviors, were also identified and observed. The secondary structures containing Dox-loaded mixed micelles had an outstanding antitumor efficacy in human lung cancer A549 cells-bearing nude mice, while little toxicities occurred or interfered with the hepatic or renal functions after the treatments. Thus, these pH-tunable α-helix-containing mixed micelles are innovative and promising for controlled intracellular anticancer drug delivery.

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Aib-containing peptide analogs: Cellular uptake and utilization in oligonucleotide delivery

Cited by 15 publications

References 22 publications

Antisense Oligonucleotide-based Splice Correction for USH2A-associated Retinal Degeneration Caused by a Frequent Deep-intronic Mutation

Antisense Oligonucleotide-based Splice Correction for USH2A-associated Retinal Degeneration Caused by a Frequent Deep-intronic Mutation

Isolation, Structure Elucidation, and Conformational Regulation of Myropeptins, Lipopeptides from the Fungus Myrothecium roridum

A Novel pH-Tunable Secondary Conformation Containing Mixed Micellar System in Anticancer Treatment

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