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Synthetic Control of Tertiary Helical Structures in Short Peptides.

ABSTRACT: Helical secondary and tertiary motifs are commonly observed as binding epitopes in natural and engineered protein scaffolds. While several strategies have been described to constrain ?-helices or reproduce their binding attributes in synthetic mimics, general strategies to mimic tertiary helical motifs remain in their infancy. We recently described a synthetic strategy to develop helical dimers ( J. Am. Chem. Soc. 2015, 137, 11618-11621). We found that replacement of an interhelical salt bridge with a covalent bond can stabilize antiparallel motifs in short sequences. Here we show that the approach can be generalized to obtain antiparallel and parallel dimers as well as trimer motifs. Helical stabilization requires judiciously designed cross-linkers as well as optimal interhelical hydrophobic packing. We anticipate that these mimics would afford new classes of modulators of biological function.

SUBMITTER: Wuo MG

PROVIDER: S-EPMC7768809 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Synthetic Control of Tertiary Helical Structures in Short Peptides.

Wuo Michael G MG Hong Seong Ho SH Singh Arunima A Arora Paramjit S PS

Journal of the American Chemical Society 20181114 47

Helical secondary and tertiary motifs are commonly observed as binding epitopes in natural and engineered protein scaffolds. While several strategies have been described to constrain α-helices or reproduce their binding attributes in synthetic mimics, general strategies to mimic tertiary helical motifs remain in their infancy. We recently described a synthetic strategy to develop helical dimers ( J. Am. Chem. Soc. 2015, 137, 11618-11621). We found that replacement of an interhelical salt bridge ...[more]

PMID: 30395711

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