title: Solvent polarity controls the helical conformation of short peptides rich in Calpha-tetrasubstituted amino acids.
abstract: The two peptides, rich in C(alpha)-tetrasubstituted amino acids, Ac-[Aib-L-(alphaMe)Val-Aib](2)-L-His-NH(2) (1) and Ac-[Aib-L-(alphaMe)Val-Aib](2)-O-tBu (2 a) are prevalently helical. They present the unique property of changing their conformation from the alpha- to the 3(10)-helix as a function of the polarity of the solvent: alpha in more polar solvents, 3(10) in less polar ones. Conclusive evidence of this reversible change of conformation is reported on the basis of the circular dichroism (CD) spectra and a detailed two-dimensional NMR analysis in two solvents (trifluoroethanol and methanol) refined with molecular dynamics calculations. The X-ray diffractometric analysis of the crystals of both peptides reveals that they assume a prevalent 3(10)-helix conformation in the solid state. This conformation is practically superimposable on that obtained from the NMR analysis of 1 in methanol. The NMR results further validate the reported CD signature of the 3(10)-helix and the use of the CD technique for its assessment.
authors.affiliation: University of Padova, Department of Chemical Sciences, 35131 Padova, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bellanda
authors.forename: Stefano
authors.initials: S
authors.lastname: Mammi
authors.forename: Silvano
authors.initials: S
authors.lastname: Geremia
authors.forename: Nicola
authors.initials: N
authors.lastname: Demitri
authors.forename: Lucio
authors.initials: L
authors.lastname: Randaccio
authors.forename: Quirinus B
authors.initials: QB
authors.lastname: Broxterman
authors.forename: Bernard
authors.initials: B
authors.lastname: Kaptein
authors.forename: Paolo
authors.initials: P
authors.lastname: Pengo
authors.forename: Lucia
authors.initials: L
authors.lastname: Pasquato
authors.forename: Paolo
authors.initials: P
authors.lastname: Scrimin
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D000432:Methanol / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012997:Solvents / Q000737:chemistry*; D013696:Temperature; D014270:Trifluoroethanol / Q000737:chemistry
chemical_list: D000596:Amino Acids; D009842:Oligopeptides; D012997:Solvents; C483755:acetyl-aminoisobutyryl-alpha-methylvalyl-aminoisobutyryl-aminoisobutyryl-alpha-methylvalyl-aminoisobutyryl-histidinamide; D014270:Trifluoroethanol; D000432:Methanol