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The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic ?-strands.

ABSTRACT: Pentapeptides having the sequence R-HN-Ala-Val-X-Val-Leu-OMe, where the central residue X is L-serine, L-threonine, (2S,3R)-L-CF3-threonine and (2S,3S)-L-CF3-threonine were prepared. The capacity of (2S,3S)- and (2S,3R)-CF3-threonine analogues to stabilize an extended structure when introduced in the central position of pentapeptides is demonstrated by NMR conformational studies and molecular dynamics simulations. CF3-threonine containing pentapeptides are more prone to mimic ?-strands than their natural Ser and Thr pentapeptide analogues. The proof of concept that these fluorinated ?-strand mimics are able to disrupt protein-protein interactions involving ?-sheet structures is provided. The CF3-threonine containing pentapeptides interact with the amyloid peptide A?1-42 in order to reduce the protein-protein interactions mediating its aggregation process.

SUBMITTER: Xu Y

PROVIDER: S-EPMC5753055 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands.

Xu Yaochun Y Correia Isabelle I Ha-Duong Tap T Kihal Nadjib N Soulier Jean-Louis JL Kaffy Julia J Crousse Benoît B Lequin Olivier O Ongeri Sandrine S

Beilstein journal of organic chemistry 20171221

Pentapeptides having the sequence R-HN-Ala-Val-X-Val-Leu-OMe, where the central residue X is L-serine, L-threonine, (2S,3R)-L-CF3-threonine and (2S,3S)-L-CF3-threonine were prepared. The capacity of (2S,3S)- and (2S,3R)-CF3-threonine analogues to stabilize an extended structure when introduced in the central position of pentapeptides is demonstrated by NMR conformational studies and molecular d ...[more]

PMID: 29564012

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