Conformational properties and aggregation of homo-oligomeric β 3 (R)-valine peptides in organic solvents.

The conformational characteristics of protected homo-oligomeric Boc-[β3 (R)Val]n -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 1 H NMR analysis of Boc-[β3 (R)Val]12 -OMe reveals that the peptide aggregates extensively in CDCl3 , but is disaggregated in 20%, (v/v) dimethyl sulfoxide (DMSO) in CDCl3 and in CD3 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 CHCl3 establishes that the onset of folding and aggregation, as evidenced by NH stretching bands at 3375 cm-1 (intramolecular) and 3285 cm-1 (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]n -NHMe, ω = α, β, and γ and n = 1, 2, and 3. Analysis of the FTIR spectra in CHCl3 , 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.