title: Capping β-hairpin with N-terminal d-amino acid stabilizes peptide scaffold.
abstract: Various strategies exist to stabilize de novo designed synthetic peptide β-hairpins or β-sheets structures, especially at the non-hydrogen bonding position. However, strategies to stabilize strand termini, which are affected by fraying, are highly limited. Here, by substituting N-terminal aliphatic amino acid with its mirror image counterpart, we achieve a significant increase in scaffold stabilization, resulting from the formation of a terminal aliphatic-aromatic hydrophobic CH…pi cluster. Our extensive solution NMR studies support the incorporation of an N-terminal d-aliphatic amino acid in the design of short β-hairpins, while successfully retaining the overall structural scaffold. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 260-266, 2016.
authors.affiliation: Molecular Biophysics Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, 462023, Madhya Pradesh, India.
authors.forename: Kamlesh M
authors.initials: KM
authors.lastname: Makwana
authors.affiliation: Molecular Biophysics Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, 462023, Madhya Pradesh, India.
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Mahalakshmi
mesh_terms: D000595:Amino Acid Sequence; D005449:Fluorenes / Q000737:chemistry; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007930:Leucine / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis*; D000072757:Protein Conformation, beta-Strand; D017510:Protein Folding; D055550:Protein Stability; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*; D012996:Solutions
chemical_list: D005449:Fluorenes; D010455:Peptides; D012996:Solutions; D007930:Leucine
keywords: NMR spectroscopy; aliphatic-aromatic cluster; d-amino acid; peptide design; peptide β-hairpin