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Comparison of Design Strategies for Promotion of β‐Peptide 14‐Helix Stability in Water
Author(s) -
Vaz Esther,
Pomerantz William C.,
Geyer Matthias,
Gellman Samuel H.,
Brunsveld Luc
Publication year - 2008
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200800355
Subject(s) - side chain , salt bridge , chemistry , peptide , folding (dsp implementation) , ionic strength , helix (gastropod) , ionic bonding , salt (chemistry) , covalent bond , aqueous solution , combinatorial chemistry , stereochemistry , cyclic peptide , crystallography , organic chemistry , ion , polymer , ecology , biochemistry , biology , snail , mutant , electrical engineering , gene , engineering
Many short β‐peptides adopt well‐defined conformations in organic solvents, but specialized stabilizing elements are required for folding to occur in aqueous solution. Several different strategies to stabilize the 14‐helical secondary structure in water have been developed, and here we provide a direct comparison of three such strategies. We have synthesized and characterized β‐peptide heptamers in which variously a salt bridge between side chains, a covalent link between side chains, or two cyclically constrained residues have been incorporated to promote 14‐helicity. The incorporation of a salt bridge does not generate significant 14‐helicity in water, according to CD and 2D NMR data. In contrast, incorporation either of a lactam bridge between side chains or of cyclic residues results in stable 14‐helices in water. The β‐peptides featuring trans ‐2‐aminocyclohexanecarboxylic acid (ACHC) residues show the highest 14‐helical backbone stability, with hardly any sensitivity to pH or ionic strength. The β‐peptides featuring side‐chain‐to‐side‐chain cyclization show lower 14‐helical backbone stability and higher sensitivity to pH and ionic strength, but increased order between the side chains because of the cyclization.