title: Conformational properties and aggregation of homo-oligomeric β3(R)-valine peptides in organic solvents.
abstract: 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 detailed1H 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 CDCl3and 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 CHCl3establishes 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.
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560 012, India.
authors.forename: Basavalingappa
authors.initials: B
authors.lastname: Vasantha
authors.affiliation: NMR Research Center, Indian Institute of Science, Bangalore, 560 012, India.
authors.forename: Hunashal
authors.initials: H
authors.lastname: Yamanappa
authors.affiliation: NMR Research Center, Indian Institute of Science, Bangalore, 560 012, India.
authors.forename: Srinivasarao
authors.initials: S
authors.lastname: Raghothama
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560 012, India.
authors.forename: Padmanabhan
authors.initials: P
authors.lastname: Balaram
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D002942:Circular Dichroism; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides / Q000737:chemistry*; D009930:Organic Chemicals / Q000737:chemistry; D066329:Protein Aggregates; D011487:Protein Conformation; D017510:Protein Folding; D012997:Solvents / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D014633:Valine / Q000737:chemistry*
chemical_list: D009842:Oligopeptides; D009930:Organic Chemicals; D066329:Protein Aggregates; C080708:R peptide; D012997:Solvents; D014633:Valine
keywords: 14-helix; and γ peptides; oligo-β-valines; peptide conformation; α; β; β-peptide aggregation; β-peptides