title: Helix and hairpin nucleation in short peptides using centrally positioned conformationally constrained dipeptide segments.
abstract: The effect of incorporation of a centrally positioned Ac(6)c-Xxx segment where Xxx = (L)Val/(D)Val into a host oligopeptide composed of l-amino acid residues has been investigated. Studies of four designed octapeptides Boc-Leu-Phe-Val-Ac(6)c-Xxx-Leu-Phe-Val-OMe (Xxx = (D)Val 1, (L)Val 2) Boc-Leu-Val-Val-Ac(6)c-Xxx-Leu-Val-Val-OMe (Xxx = (D)Val 3, (L)Val 4) are reported. Diagnostic nuclear Overhouse effects characteristic of hairpin conformations are observed for Xxx = (D)Val peptides (1 and 3) while continuous helical conformation characterized by sequential N(i)H ↔ N(i+1)H NOEs are favored for Xxx = (L)Val peptides (2 and 4) in methanol solutions. Temperature co-efficient of NH chemical shifts are in agreement with distinctly different conformational preferences upon changing the configuration of the residue at position 5. Crystal structures of peptides 2 and 4 (Xxx = (L)Val) establish helical conformations in the solid state, in agreement with the structures deduced from NMR data. The results support the design principle that centrally positioned type I β-turns may be used to nucleate helices in short peptides, while type I'β-turns can facilitate folding into β-hairpins.
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India.
authors.forename: Siddappa
authors.initials: S
authors.lastname: Chandrappa
authors.forename: Subrayashastry
authors.initials: S
authors.lastname: Aravinda
authors.forename: Srinivasarao
authors.initials: S
authors.lastname: Raghothama
authors.forename: Rajesh
authors.initials: R
authors.lastname: Sonti
authors.forename: Rajkishor
authors.initials: R
authors.lastname: Rai
authors.forename: Veldore V
authors.initials: VV
authors.lastname: Harini
authors.forename: Narayanaswamy
authors.initials: N
authors.lastname: Shamala
authors.forename: Padmanabhan
authors.initials: P
authors.lastname: Balaram
mesh_terms: D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D004151:Dipeptides; D010455:Peptides