Work

Impact of Strand Edge N-Amination on the Stability of a Parallel β-Hairpin Fold

Year: 2025

Type: article

Abstract: Peptide backbone N-amination has emerged as a useful strategy to stabilize antiparallel β-sheet structure. Here, we used circular dichroism and NMR to evaluate the impact of amide-to-hydrazide substitution on the folded population of a parallel β-hairpin model. Outer-edge N-amination was well tolerated and resulted in enhanced stability relative to N-methylation. High-resolution NMR structures confirmed that the α-hydrazino acid residues adopt canonical parallel β-strand torsions that are compatible with the formation of intraresidue C6 hydrogen bonds involving the hydrazide NH 2 group.

Source: The Journal of Organic Chemistry

DOI: 10.1021/acs.joc.5c02479

Authors: Syrah K. Starnes, W. Seth Horne, Juan R. Del Valle

Institutions: University of Notre Dame, University of Pittsburgh

Language: English

Topic: Chemical Synthesis and Analysis

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Institute on Aging, National Institute of General Medical Sciences, Division of Chemistry

Awards: G1007111735, G2272136557, G3959159847, Chemical approaches to selectively target beta-rich amyloids