Low pH-triggering changes in peptide secondary structures

Furukawa, Kaori; Oba, Makoto; Toyama, Kotomi; Opiyo, George Ouma; Demizu, Yosuke; Kurihara, Masaaki; Doi, Mitsunobu; Tanaka, Masakazu

doi:10.1039/c7ob01374d

Cited by 7 publications

(6 citation statements)

References 35 publications

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“…A chiral center at the tethered side chain was previously reported to induce the helical structures of l ‐α‐amino acid peptides, and this strategy may be applied to the enhancement of target binding affinity . The chiral acetal moiety in the ( R , R )‐Ac 4 c 3BD was changeable and may also be used for low pH‐triggering structural changes . Therefore, precisely elucidated helical secondary structures may be invaluable for designing organo‐catalysts, cell‐penetrating peptides, and target‐binding peptides …”

Section: Figurementioning

confidence: 99%

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Diastereomeric Right‐ and Left‐Handed Helical Structures with Fourteen (R)‐Chiral Centers

Eto

Oba

Ueda

et al. 2017

Chemistry A European J

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The relationship between chiral centers and the helical-screw control of their peptides has already been reported, but it has yet to be elucidated in detail. A chiral four-membered ring α,α-disubstituted α-amino acid with a (R,R)-butane-2,3-diol acetal moiety at the γ-position, but no α-chiral carbon, was synthesized. X-ray crystallographic analysis unambiguously revealed that its homo-chiral heptapeptide formed right-handed (P) and left-handed (M) 3 -helical structures at a ratio of 1:1. They appeared to be enantiomeric at the peptide backbone, but diastereomeric with fourteen (R)-configuration chiral centers. Conformational analyses of homopeptides in solution also indicated that diastereomeric (P) and (M) helices existed at approximately equal amounts, with a slight preference toward right-handedness, and they quickly interchanged at room temperature. The circumstances of chiral centers are important for the control of their helical-screw direction.

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Section: Figurementioning

confidence: 99%

“…[24] The chiral acetal moiety in the (R,R)-Ac 4 c 3BD was changeable and may also be used for low pH-triggerings tructural changes. [25] Therefore, precisely elucidated helical secondary structures may be invaluable for designing organo-catalysts, [26] cell-penetrating peptides, [27] and targetbinding peptides. [24] .…”

mentioning

confidence: 99%

Diastereomeric Right‐ and Left‐Handed Helical Structures with Fourteen (R)‐Chiral Centers

Eto

Oba

Ueda

et al. 2017

Chemistry A European J

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“…This creates an interesting conformational switch, in which the changes in the geometry of the amino acid residue can result in changes in the 3-dimensional structure of the peptide. The described imidazole-amino acids can be applied, potentially, to design pH-sensitive peptides for targeting acidic tissues (Furukawa et al 2017;Weerakkody et al 2013), or to use cell surface acidity as a feature that can be exploited using pH-sensitive peptide folding to target agents to diseased cell surfaces or cytoplasms (Reshetnyak al. 2020).…”

Section: Discussionmentioning

confidence: 99%

Imidazole-amino acids. Conformational switch under tautomer and pH change

2022

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Replacement of the main chain peptide bond by imidazole ring seems to be a promising tool for the peptide-based drug design, due to the specific prototropic tautomeric as well as amphoteric properties. In this study, we present that both tautomer and pH change can cause a conformational switch of the studied residues of alanine (1–4) and dehydroalanine (5–8) with the C-terminal peptide group replaced by imidazole. The DFT methods are applied and an environment of increasing polarity is simulated. The conformational maps (Ramachandram diagrams) are presented and the stability of possible conformations is discussed. The neutral forms, tautomers τ (1) and π (2), adapt the conformations αRτ (φ, ψ = − 75°, − 114°) and C7eq (φ, ψ = − 75°, 66°), respectively. Their torsion angles ψ differ by about 180°, which results in a considerable impact on the peptide chain conformation. The cation form (3) adapts both these conformations, whereas the anion analogue (4) prefers the conformations C5 (φ, ψ = − 165°, − 178°) and β2 (φ, ψ ~ − 165°, − 3°). Dehydroamino acid analogues, the tautomers τ (5) and π (6) as well as the anion form (8), have a strong tendency toward the conformations β2 (φ, ψ = − 179°, 0°) and C5 (φ, ψ = − 180°, 180°). The preferences of the protonated imidazolium form (7) depend on the environment. The imidazole ring, acting as a donor or acceptor of the hydrogen bonds created within the studied residues, has a profound effect on the type of conformation.

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“…The peptide, including the dAA side chain, is stabilized as an α-helix structure. However, structural changes in dAA induced by low pH affects the changes in the secondary structure of the peptide from an α-helix to a random coil [74]. The hydrophobic peptide -YVIFL- also demonstrates pH-dependent structural changes.…”

Section: Factors For Peptide Self-assemblymentioning

confidence: 99%

Self-Assembling Peptides and Their Application in the Treatment of Diseases

Lee

Trinh

Yoo

et al. 2019

IJMS

166

122

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Self-assembling peptides are biomedical materials with unique structures that are formed in response to various environmental conditions. Governed by their physicochemical characteristics, the peptides can form a variety of structures with greater reactivity than conventional non-biological materials. The structural divergence of self-assembling peptides allows for various functional possibilities; when assembled, they can be used as scaffolds for cell and tissue regeneration, and vehicles for drug delivery, conferring controlled release, stability, and targeting, and avoiding side effects of drugs. These peptides can also be used as drugs themselves. In this review, we describe the basic structure and characteristics of self-assembling peptides and the various factors that affect the formation of peptide-based structures. We also summarize the applications of self-assembling peptides in the treatment of various diseases, including cancer. Furthermore, the in-cell self-assembly of peptides, termed reverse self-assembly, is discussed as a novel paradigm for self-assembling peptide-based nanovehicles and nanomedicines.

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Low pH-triggering changes in peptide secondary structures

Abstract: An acidic treatment of cyclic α,α-disubstituted α-amino acid-containing peptides changes their conformation from a helical to a random structure.

Cited by 7 publications

References 35 publications

Diastereomeric Right‐ and Left‐Handed Helical Structures with Fourteen (R)‐Chiral Centers

Diastereomeric Right‐ and Left‐Handed Helical Structures with Fourteen (R)‐Chiral Centers

Imidazole-amino acids. Conformational switch under tautomer and pH change

Self-Assembling Peptides and Their Application in the Treatment of Diseases

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