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

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• 作者：Irene Maffucci ; Jonathan Clayden ; Alessandro Contini
• 刊名：Journal of Physical Chemistry B
• 出版年：2015
• 出版时间：November 5, 2015
• 年：2015
• 卷：119
• 期：44
• 页码：14003-14013
• 全文大小：738K
• ISSN：1520-5207

文摘

The mechanisms behind the propensity of chiral constrained C伪-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 (鈭?i>x, +y, +z) or (+x, +y, 鈭?i>z) sectors of a right-handed 3D Cartesian space, where the z axis corresponds to the axis of the helix and the C伪 lies on the +y semiaxis (0, +y, 0). The different strengthening of the noncovalent interactions, also comprising C鈥揌路路路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.