Design of cyclic RGD-conjugated Aib-containing amphipathic helical peptides for targeted delivery of small interfering RNA

Wada, Shun‐ichi; Iwata, Masashi; Ozaki, Yuka; Ozaki, Takuo; Hayashi, Junsuke; Urata, Hidehito

doi:10.1016/j.bmc.2016.07.040

Cited by 18 publications

(30 citation statements)

References 22 publications

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“…A quinoline-based aromatic foldamer was reported to cross the cell membrane despite its anionic nature 12 . It is also worth noting that foldamers are able to deliver not only low-molecular-weight compounds such as fluorescein but also biomacromolecules such as nucleic acids into cells in vitro 13–16 . We previously reported CPP foldamers containing α,α-disubstituted α-amino acids (dAAs) 17–21 .…”

Section: Introductionmentioning

confidence: 99%

Secondary structures and cell-penetrating abilities of arginine-rich peptide foldamers

Oba

Nagano

Kato

et al. 2019

Sci Rep

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Foldamers, which are folded oligomers with well-defined conformations, have been recently reported to have a good cell-penetrating ability. α,α-Disubstituted α-amino acids are one such promising tool for the design of peptide foldamers. Here, we prepared four types of L-arginine-rich nonapeptides containing L-leucine or α,α-disubstituted α-amino acids, and evaluated their secondary structures and cell-penetrating abilities in order to elucidate a correlation between them. Peptides containing α,α-disubstituted α-amino acids had similar resistance to protease digestion but showed different secondary structures. Intracellular uptake assays revealed that the helicity of peptides was important for their cell-penetrating abilities. These findings suggested that a peptide foldamer with a stable helical structure could be promising for the design of cell-penetrating peptides.

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Section: Introductionmentioning

confidence: 99%

Secondary structures and cell-penetrating abilities of arginine-rich peptide foldamers

Oba

Nagano

Kato

et al. 2019

Sci Rep

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“…In this structure, basic amino acid residues, Lys residues, were located on the hydrophilic face of the helix, and neutral and hydrophobic amino acid residues, Leu, Ala, and Aib residues, were located on the hydrophobic face. [6,7,12] Truncated peptides from which Aib (U), Leu-Aib (LU), and Lys-Leu-Aib (KLU) residues were removed from the Cterminus of the helical peptide were synthesized by Fmoc-based solid-phase synthesis, as previously reported. [6] The Gly-Cys residues at the C-terminus are necessary for the conjugation of cRGD.…”

Section: Synthesis Of Truncated Peptides Pi Pii and Piiimentioning

confidence: 99%

“…MAP(Aib)-cRGD possesses important requisites for an RNA carrier, such as high cell membrane permeability, protection against RNA degradation by hydrolytic enzymes, and specific interaction with cancer cells. [6,9,10] In fact, we have reported that MAP(Aib)-cRGD conducts the targeted delivery of siRNA into cancer cells, A549 cells followed by the knockdown of luciferase expression in luciferase-expressing cells, [6] and the delivery of microRNA-133b and microRNA-145, which are anti-oncomiR, into WiDr or DLD-1 cells, which resulted in the repression of various endogenous protein expression. [9,10] StructureÀ activity relationship studies of MAP(Aib)-cRGD as a carrier for RNA delivery into cells have indicated that increasing the number of basic Lys residues in the amphipathic helix, [9] and truncated peptides containing 16, 12, and 8 amino acid residues The Aib-containing amphipathic peptides were conjugated with cRGDfC [cyclo(-Arg-Gly-Asp-D-Phe-Cys-)] through the formation of a disulfide bond.…”

Section: Introductionmentioning

confidence: 99%

Influence of Aib‐Containing Amphipathic Helical Chain Length in MAP(Aib)‐cRGD as Carrier for siRNA Delivery

Wada

Shibaike

Hayashi

et al. 2021

Chemistry & Biodiversity

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MAP(Aib)-cRGD, which is a conjugate of an α-aminoisobutyric acid (Aib)-containing amphipathic helical peptide [MAP(Aib)] with a α v β 3 integrin binding ligand, cRGD, at the C-terminus of the helical peptide, has been developed for siRNA delivery into cells. In this work, we synthesized three peptides containing 19 (PI), 18 (PII), and 17 (PIII) amino acid residues in the helical peptide, which lack Aib, Leu-Aib, and Lys-Leu-Aib residues present in the C-terminus of the helical peptide of the parent MAP(Aib)-cRGD, respectively. MAP(Aib)-cRGD showed the siRNA delivery into cells and the RNAi effect both in the presence and in the absence of serum in reaction media. In contrast, PI delivered siRNA into cells, and this was followed by the RNAi effect in only serum-free reaction media. On the other hand, siRNA delivery was abolished by the further reduction of the number of residues (PII and PIII) in the C-terminus. Our data indicate that the Aib-containing helical part requires 20 residues in the conjugation of the helical peptide with cRGD for the construction of carrier for siRNA delivery into cells.

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“…The CPP-peptide conjugates have been extensively studied. It has been demonstrated that the addition of CPPs to variously structured peptides, such as α helix 174,175 and β sheet (Figure 9B) 176,177, helps the internalization of the nanostructures. Wada et al proposed the location and the number of TAT peptides in the conjugates perhaps structurally related to the cellular uptake of the CPP-peptide/siRNA complexes 174,175.…”

Section: Applications Of Self-assembling Cpp Conjugates For Intracmentioning

confidence: 99%

“…It has been demonstrated that the addition of CPPs to variously structured peptides, such as α helix 174,175 and β sheet (Figure 9B) 176,177, helps the internalization of the nanostructures. Wada et al proposed the location and the number of TAT peptides in the conjugates perhaps structurally related to the cellular uptake of the CPP-peptide/siRNA complexes 174,175. Hategan et al reported that addition of TAT peptides to amyloid-β fibrils enhanced rigidity and mechanical resistances of the complexes by increasing β sheet conformations, accompanying with morphological changes and augmented neurotoxicity 178.…”

Section: Applications Of Self-assembling Cpp Conjugates For Intracmentioning

confidence: 99%

Advances in intracellular delivery through supramolecular self-assembly of oligonucleotides and peptides

et al. 2019

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Cells utilize natural supramolecular assemblies to maintain homeostasis and biological functions. Naturally inspired modular assembly of biomaterials are now being exploited for understanding or manipulating cell biology for treatment, diagnosis, and detection of diseases. Supramolecular biomaterials, in particular peptides and oligonucleotides, can be precisely tuned to have diverse structural, mechanical, physicochemical and biological properties. These merits of oligonucleotides and peptides as building blocks have given rise to the evolution of numerous nucleic acid- and peptide-based self-assembling nanomaterials for various medical applications, including drug delivery, tissue engineering, regenerative medicine, and immunotherapy. In this review, we provide an extensive overview of the intracellular delivery approaches using supramolecular self-assembly of DNA, RNA, and peptides. Furthermore, we discuss the current challenges related to subcellular delivery and provide future perspectives of the application of supramolecular biomaterials for intracellular delivery in theranostics.

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Design of cyclic RGD-conjugated Aib-containing amphipathic helical peptides for targeted delivery of small interfering RNA

Cited by 18 publications

References 22 publications

Secondary structures and cell-penetrating abilities of arginine-rich peptide foldamers

Secondary structures and cell-penetrating abilities of arginine-rich peptide foldamers

Influence of Aib‐Containing Amphipathic Helical Chain Length in MAP(Aib)‐cRGD as Carrier for siRNA Delivery

Advances in intracellular delivery through supramolecular self-assembly of oligonucleotides and peptides

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