Premium
Comparative α‐Helicity of Cyclic Pentapeptides in Water
Author(s) -
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.
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201310245
Subject(s) - pentapeptide repeat , helicity , helix (gastropod) , circular dichroism , stereochemistry , chemistry , linker , peptidomimetic , nuclear magnetic resonance spectroscopy , peptide , residue (chemistry) , combinatorial chemistry , biochemistry , biology , physics , ecology , particle physics , snail , computer science , operating system
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 1 –X 5 ) were compared here, using circular dichroism and 2D NMR spectroscopy, for α‐helix induction in simple model pentapeptides, Ac‐cyclo(1,5)‐[X 1 ‐Ala‐Ala‐Ala‐X 5 ]‐NH 2 , 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 10 ‐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.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom