title: Origin of Helical Screw Sense Selectivity Induced by Chiral Constrained Cα-Tetrasubstituted α-Amino Acids in Aib-based Peptides.
abstract: The mechanisms behind the propensity of chiral constrained Cα-tetrasubstituted amino acids (cCTAAs) to induce one particular helical screw sense, when included in the Ac-Aib2-cCTAA-Aib2-NHMe peptide model, were studied through replica exchange molecular dynamics, potential of mean force, and quantum theory of atoms in molecules calculations. We observed that cCTAAs exert their effect on helical screw sense selectivity through the positioning of the side chain to generate steric hindrance in either the (-x, +y, +z) or (+x, +y, -z) sectors of a right-handed 3D Cartesian space, where the z axis corresponds to the axis of the helix and the Cα lies on the +y semiaxis (0, +y, 0). The different strengthening of the noncovalent interactions, also comprising C-H···O interactions, exerted by the cCTAA in the right-handed or left-handed helix was also found important to define the preference of a cCTAA for a particular helix screw sense.
authors.affiliation: Dipartimento di Scienze Farmaceutiche - Sezione di Chimica Generale e Organica "Alessandro Marchesini", Università degli Studi di Milano , Via Venezian, 21, 20133 Milano, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Maffucci
authors.affiliation: School of Chemistry, University of Manchester , Oxford Road, Manchester M13 9PL, U.K.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Clayden
authors.affiliation: Dipartimento di Scienze Farmaceutiche - Sezione di Chimica Generale e Organica "Alessandro Marchesini", Università degli Studi di Milano , Via Venezian, 21, 20133 Milano, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Contini
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D011789:Quantum Theory
chemical_list: D000596:Amino Acids; D010455:Peptides