The theoretical basis behind the ability of constrained Cα-tetrasubstituted amino acids (CTAAs) to induce stable helical conformations has been studied through Replica Exchange Molecular Dynamics Potential of Mean Force Quantum Theory of Atoms In Molecules calculations on Ac-l-Ala-CTAA-l-Ala-Aib-l-Ala-NHMe peptide models. We found that the origin of helix stabilization by CTAAs can be ascribed to at least two complementary mechanisms limiting the backbone conformational freedom: steric hindrance predominantly in the (+x,+y,–z) sector of a right-handed 3D Cartesian space, where the z axis coincides with the helical axis and the Cα of the CTAA lies on the +y axis (0,+y,0), and the establishment of additional and relatively strong C–H···O interactions involving the CTAA.

Mechanism of stabilization of helix secondary structure by constrained Cα-tetrasubstituted alpha-amino acids / I. Maffucci, S. Pellegrino, J. Clayden, A. Contini. - In: JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL. - ISSN 1520-6106. - 119:4(2015), pp. 1350-1361. [10.1021/jp510775e]

Mechanism of stabilization of helix secondary structure by constrained Cα-tetrasubstituted alpha-amino acids

I. Maffucci
Primo
;
S. Pellegrino
Secondo
;
A. Contini
2015

Abstract

The theoretical basis behind the ability of constrained Cα-tetrasubstituted amino acids (CTAAs) to induce stable helical conformations has been studied through Replica Exchange Molecular Dynamics Potential of Mean Force Quantum Theory of Atoms In Molecules calculations on Ac-l-Ala-CTAA-l-Ala-Aib-l-Ala-NHMe peptide models. We found that the origin of helix stabilization by CTAAs can be ascribed to at least two complementary mechanisms limiting the backbone conformational freedom: steric hindrance predominantly in the (+x,+y,–z) sector of a right-handed 3D Cartesian space, where the z axis coincides with the helical axis and the Cα of the CTAA lies on the +y axis (0,+y,0), and the establishment of additional and relatively strong C–H···O interactions involving the CTAA.
screw-sense preference; achiral peptide-chain; molecular-dynamics simulations; O hydrogen-bonds; force-fields; conformational preferences; linear oligopeptides; asymmetric-synthesis; AB-initio; protein
Settore CHIM/06 - Chimica Organica
Settore CHIM/02 - Chimica Fisica
Sintesi e applicazioni biomediche di peptidomimetici in campo oncologico
20-dic-2014
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/263554
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