Trp-Trp Cross-Linking: A Structure-Reactivity Relationship in the Formation and Design of Hyperstable Peptide β-Hairpin and α-Helix Scaffolds.
Using model peptide β-hairpin scaffolds, the facile formation of a remarkably stable covalently cross-linked modification is reported in the tryptophan side chain, which confers hyperstability to the scaffold and displays a unique structure-reactivity relationship. This strategy is also validated to obtain a thermostable α-helix. Such imposition of conformational constraints can have versatile applications in peptide-based drug discovery, and this strategy may improve peptide bioavailability.
Molecular Biophysics Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal 462023, India.
Kamlesh M
KM
Makwana
Molecular Biophysics Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal 462023, India.
Radhakrishnan
R
Mahalakshmi
D000595:Amino Acid Sequence; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000737:chemistry*
D010455:Peptides; D014364:Tryptophan