Right-handed 14-helix in β3-peptides from L-aspartic acid monomers

beta-Peptides made from L-aspartic acid monomers form a new class of beta(3)-peptides. Here we report the first three-dimensional NMR solution structure of a beta(3)-hexapeptide (1) from L-aspartic acid monomers in 2,2,2-trifluoroethanol (TFE). We show that 1 forms a right-handed 14-helical structure in TFE. alpha-peptides from naturally occurring L-amino acids adopt a right-handed alpha-helix whereas p beta(3)-peptides formed from beta(3)-amino acids derived from naturally occurring L-amino acids form left-handed 14-helices. The right-handed 14-helical conformation of I is a better mimic of alpha-peptide conformations. Using the NMR structure of 1 in TFE, we further study the conformation of 1 in water, as well as two similar 0 beta(3)-peptides (2 and 3) in water and TFE by molecular dynamics (MD) simulations. NMR and MD results suggest loss of secondary structure of 1 in water and show that it forms a fully extended structure. 2 and 3 contain residues with oppositely charged side chains that engage in salt-bridge interactions and dramatically stabilize the 14-helical conformation in aqueous media. (c) 2008 Elsevier B.V. All rights reserved.