title: Synthesis of C-linked carbo-β2-amino acids and β2-peptides: design of new motifs for left-handed 12/10- and 10/12-mixed helices.
abstract: C-linked carbo-β(2)-amino acids (β(2)-Caa), a new class of β-amino acid with a carbohydrate side chain having d-xylo configuration, were prepared from d-glucose. The main idea behind the design of the new β-amino acids was to move the steric strain of the bulky carbohydrate side chain from the Cβ- to the Cα-carbon atom and to explore its influence on the folding propensities in peptides with alternating (R)- and (S)-β(2)-Caas. The tetra- and hexapeptides derived were studied employing NMR (in CDCl(3)), CD, and molecular dynamics simulations. The β(2)-peptides of the present study form left-handed 12/10- and 10/12-mixed helices independent of the order of the alternating chiral amino acids in the sequence and result in a new motif. These results differ from earlier findings on β(3)-peptides of the same design, containing a carbohydrate side chain with d-xylo configuration, which form exclusively right-handed 12/10-mixed helices. Quantum chemical calculations employing ab initio MO theory suggest the side chain chirality as an important factor for the observed definite left- or right-handedness of the helices in the β(2)- and β(3)-peptides.
authors.affiliation: Organic and Biomolecular Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad-500 007, India.
authors.forename: Gangavaram V M
authors.initials: GV
authors.lastname: Sharma
authors.forename: Nelli Yella
authors.initials: NY
authors.lastname: Reddy
authors.forename: Rapolu
authors.initials: R
authors.lastname: Ravi
authors.forename: Bommagani
authors.initials: B
authors.lastname: Sreenivas
authors.forename: Gattu
authors.initials: G
authors.lastname: Sridhar
authors.forename: Deepak
authors.initials: D
authors.lastname: Chatterjee
authors.forename: Ajit C
authors.initials: AC
authors.lastname: Kunwar
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Hofmann
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis*; D002942:Circular Dichroism; D005947:Glucose / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000138:chemical synthesis*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011789:Quantum Theory; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D010455:Peptides; D005947:Glucose