Right-handed 14-helix in beta 3-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 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 1 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 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.
Kaur
Kamaljit
K
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada T6G 2N8. kkaur@ualberta.ca
Sprules
Tara
T
Soliman
Wael
W
Beleid
Reem
R
Ahmed
Sahar
S
D001224:Aspartic Acid / Q000737:chemistry*; D003198:Computer Simulation; D019281:Dimerization; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary
D010455:Peptides; D001224:Aspartic Acid