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.

Origin of Helical Screw Sense Selectivity Induced by Chiral Constrained Cα-Tetrasubstituted α-Amino Acids in Aib-based Peptides / I. Maffucci, J. Clayden, A. Contini. - In: JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL. - ISSN 1520-6106. - 119:44(2015 Nov 05), pp. 14003-14013. [10.1021/acs.jpcb.5b07050]

Origin of Helical Screw Sense Selectivity Induced by Chiral Constrained Cα-Tetrasubstituted α-Amino Acids in Aib-based Peptides

I. Maffucci
Primo
;
A. Contini
2015-11-05

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.
Amino Acids; Molecular Dynamics Simulation; Molecular Structure; Peptides; Quantum Theory; Physical and Theoretical Chemistry; Materials Chemistry2506 Metals and Alloys; Surfaces, Coatings and Films; Medicine (all)
Settore CHIM/06 - Chimica Organica
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/429504
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