Comparative α-helicity of cyclic pentapeptides in water.
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.
Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072 (Australia).
Aline D
AD
de Araujo
Huy N
HN
Hoang
W Mei
WM
Kok
Frederik
F
Diness
Praveer
P
Gupta
Timothy A
TA
Hill
Russell W
RW
Driver
David A
DA
Price
Spiros
S
Liras
David P
DP
Fairlie
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013696:Temperature; D014867:Water / Q000737:chemistry*
D009842:Oligopeptides; D010456:Peptides, Cyclic; D014867:Water
NMR structure; circular dichroism; cyclic peptides; helix induction; α-helix