TY - JOUR
T1 - Comparison of design strategies for promotion of ß-peptide 14-helix stability in water
AU - Vaz, E.
AU - Pomerantz, W.C.
AU - Geyer, M.
AU - Gellman, S.H.
AU - Brunsveld, L.
PY - 2008
Y1 - 2008
N2 - Many short -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 -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 -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 -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.
AB - Many short -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 -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 -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 -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.
U2 - 10.1002/cbic.200800355
DO - 10.1002/cbic.200800355
M3 - Article
SN - 1439-4227
VL - 9
SP - 2254
EP - 2259
JO - ChemBioChem
JF - ChemBioChem
IS - 14
ER -