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Rational Design and Synthesis of Right-Handed d-Sulfono-γ-AApeptide Helical Foldamers as Potent Inhibitors of Protein-Protein Interactions.

ABSTRACT: Novel unprecedented helical foldamers have been effectively designed and synthesized. The homogeneous right-handed d-sulfono-γ-AApeptides represent a new generation of unnatural helical peptidomimetics, which have similar folding conformation to α-peptides, making them an ideal molecular scaffold to design α-helical mimetics. As demonstrated with p53-MDM2 PPI as a model application, the right-handed d-sulfono-γ-AApeptides reveal much-enhanced binding affinity compared to the p53 peptide. The design of d-sulfono-γ-AApeptides may provide a new and alternative strategy to modulate protein-protein interactions.

SUBMITTER: Sang P

PROVIDER: S-EPMC8204676 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Rational Design and Synthesis of Right-Handed d-Sulfono-γ-AApeptide Helical Foldamers as Potent Inhibitors of Protein-Protein Interactions.

Sang Peng P Shi Yan Y Higbee Pirada P Wang Minghui M Abdulkadir Sami S Lu Junhao J Daughdrill Gary G Chen Jiandong J Cai Jianfeng J

The Journal of organic chemistry 20200802 16

Novel unprecedented helical foldamers have been effectively designed and synthesized. The homogeneous right-handed d-sulfono-γ-AApeptides represent a new generation of unnatural helical peptidomimetics, which have similar folding conformation to α-peptides, making them an ideal molecular scaffold to design α-helical mimetics. As demonstrated with p53-MDM2 PPI as a model application, the right-handed d-sulfono-γ-AApeptides reveal much-enhanced binding affinity compared to the p53 peptide. The des ...[more]

PMID: 32700908

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