title: Formation of periodic γ-turns in α/β-hybrid peptides: DFT and NMR experimental evidence.
abstract: Hybrid peptidic oligomers comprising natural and unnatural amino acid residues that can exhibit biomolecular folding and hydrogen-bonding mimicry have attracted considerable interest in recent years. While a variety of hybrid peptidic helices have been reported in the literature, other secondary structural patterns such as γ-turns and ribbons have not been well explored so far. The present work reports the design of novel periodic γ-turns in the oligomers of 1:1 natural-α/unnatural trans-β-norborenene (TNAA) amino acid residues. Through DFT, NMR, and MD studies, it is convincingly shown that, in the mixed conformational pool, the heterogeneous backbone of the hybrid peptides preferentially adopt periodic 8-membered (pseudo γ-turn)/7-membered (inverse γ-turn) hydrogen bonds in both polar and non-polar solvent media. It is observed that the stereochemistry and local conformational preference of the β-amino acid building blocks have a profound influence on accessing the specific secondary fold. These findings may be of significant relevance for the development of molecular scaffolds that facilitate desired positioning of functional side-chains.
authors.affiliation: Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007 (India), Fax: (+91) 40-27160512. srivaric@iict.res.in.
authors.forename: Srivari
authors.initials: S
authors.lastname: Chandrasekhar
authors.forename: Kakita Veera Mohana
authors.initials: KV
authors.lastname: Rao
authors.forename: Mallikanti
authors.initials: M
authors.lastname: Seenaiah
authors.forename: Police
authors.initials: P
authors.lastname: Naresh
authors.forename: Ambure Sharada
authors.initials: AS
authors.lastname: Devi
authors.forename: Bharatam
authors.initials: B
authors.lastname: Jagadeesh
mesh_terms: D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D010455:Peptides
keywords: NMR spectroscopy; density functional calculations; hybrid peptides; molecular dynamics; periodic γ-turns