Effects of chirality and side chain length in Cα,α-dialkylated residues on β-hairpin peptide folded structure and stability

Org Biomol Chem. 2023 Aug 9;21(31):6320-6324. doi: 10.1039/d3ob00963g.

Abstract

Strategic incorporation of achiral Cα,α-dialkylated amino acids with bulky substituents into peptides can be used to promote extended strand conformations and inhibit protein-protein interactions associated with amyloid formation. In this work, we evaluate the thermodynamic impact of chiral Cα,α monomers on folding preferences in such systems through introduction of a series of Cα-methylated and Cα-ethylated residues into a β-hairpin host sequence. Depending on stereochemical configuration of the artificial monomer and potential for additional hydrophobic packing, a Cα-ethyl-Cα-propyl glycine residue can provide similar or enhanced folded stability relative to an achiral Cα,α-diethyl analogue.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids* / chemistry
  • Glycine
  • Peptides* / chemistry
  • Protein Folding
  • Protein Structure, Secondary
  • Thermodynamics

Substances

  • Peptides
  • Amino Acids
  • Glycine