Conformational properties and aggregation of homo-oligomeric β (R)-valine peptides in organic solvents.

The conformational characteristics of protected homo-oligomeric Boc-[β (R)Val] -OMe, n = 1, 2, 3, 4, 6, 9, and 12 have been investigated in organic solvents using nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) absorption spectroscopy and circular dichroism (CD) methods. The detailed H NMR analysis of Boc-[β (R)Val] -OMe reveals that the peptide aggregates extensively in CDCl , but is disaggregated in 20%, (v/v) dimethyl sulfoxide (DMSO) in CDCl and in CD OH. Limited assignment of the N-terminus NH groups, together with solvent dependence of NH chemical shifts and temperature coefficients provides evidence for 14-helix conformation in the 12-residue peptide. FTIR analysis in CHCl establishes that the onset of folding and aggregation, as evidenced by NH stretching bands at 3375 cm (intramolecular) and 3285 cm (intermolecular), begins at the level of the tetrapeptide. The observed CD bands, 214 nm (negative) and 198 nm (positive), support 14-helix formation in the 9 and 12 residue sequences. The folding and aggregation tendencies of homo-oligomeric α-, β-, and γ- residues is compared in the model peptides Boc-[ωVal] -NHMe, ω = α, β, and γ and n = 1, 2, and 3. Analysis of the FTIR spectra in CHCl , establish that the tendency to aggregate at the di and tripeptide level follows the order β > α∼γ, while the tendency to fold follows the order γ > β > α.