Work

Synthetic Control of Tertiary Helical Structures in Short Peptides

Year: 2018

Type: article

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 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 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.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.8b10082

Authors: Michael G. Wuo, Seong Ho Hong, Arunima Singh, Paramjit S. Arora

Institution: New York University

Language: English

Topic: Chemical Synthesis and Analysis

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: New York University, National Institute of General Medical Sciences

Award: Biomolecular Recognition with Artificial Alpha-Helices