• Medientyp: E-Artikel
  • Titel: Comparative α‐Helicity of Cyclic Pentapeptides in Water
  • Beteiligte: de Araujo, Aline D.; Hoang, Huy N.; Kok, W. Mei; Diness, Frederik; Gupta, Praveer; Hill, Timothy A.; Driver, Russell W.; Price, David A.; Liras, Spiros; Fairlie, David P.
  • Erschienen: Wiley, 2014
  • Erschienen in: Angewandte Chemie International Edition
  • Sprache: Englisch
  • DOI: 10.1002/anie.201310245
  • ISSN: 1433-7851; 1521-3773
  • Schlagwörter: General Chemistry ; Catalysis
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Helix‐constrained polypeptides have attracted great interest for modulating protein–protein interactions (PPI). It is not known which are the most effective helix‐inducing strategies for designing PPI agonists/antagonists. Cyclization linkers (X<jats:sub>1</jats:sub>–X<jats:sub>5</jats:sub>) were compared here, using circular dichroism and 2D NMR spectroscopy, for α‐helix induction in simple model pentapeptides, Ac‐cyclo(1,5)‐[X<jats:sub>1</jats:sub>‐Ala‐Ala‐Ala‐X<jats:sub>5</jats:sub>]‐NH<jats:sub>2</jats:sub>, in water. In this very stringent test of helix induction, a Lys1→Asp5 lactam linker conferred greatest α‐helicity, hydrocarbon and triazole linkers induced a mix of α‐ and 3<jats:sub>10</jats:sub>‐helicity, while thio‐ and dithioether linkers produced less helicity. The lactam‐linked cyclic pentapeptide was also the most effective α‐helix nucleator attached to a 13‐residue model peptide.</jats:p>