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

The conformational characteristics of protected homo-oligomeric Boc-beta(3)(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 H-1 NMR analysis of Boc-beta(3)(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 CD3OH. 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 alpha-, beta-, and gamma-residues is compared in the model peptides Boc-omega Val] omega-NHMe, omega = alpha, beta, and gamma 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 beta > alpha similar to gamma, while the tendency to fold follows the order gamma > beta > alpha