Title: Comparative α-Helicity of Cyclic Pentapeptides in Water.
Authors: 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.
Abstract: 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 (X1-X5) were compared here, using circular dichroism and 2D NMR spectroscopy, for α-helix induction in simple model pentapeptides, Ac-cyclo(1,5)-[X1-Ala-Ala-Ala-X5]-NH2, 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 310-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.
Subjects: HELICITY (Chemistry); PEPTIDES; PROTEIN-protein interactions; CIRCULAR dichroism; NUCLEAR magnetic resonance spectroscopy; TRIAZOLES
Publication: Angewandte Chemie International Edition, 2014, Vol 53, Issue 27, p6965
ISSN: 1433-7851
Publication type: Academic Journal
DOI: 10.1002/anie.201310245

Comparative α-Helicity of Cyclic Pentapeptides in Water.

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.