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Solvent-induced conformational flexibility of a bicyclic proline analogue: Octahydroindole-2-carboxylic acid

Authors

  • Juan Torras,

    1. Departament d'Enginyeria Química, EEI, Universitat Politècnica de Catalunya, Igualada, Spain
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  • Javier G. Warren,

    1. Departamento de Química Orgánica, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), CSIC–Universidad de Zaragoza, Zaragoza, Spain
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  • Guillem Revilla-López,

    1. Departament d'Enginyeria Química, E. T. S. d'Enginyeria Industrial de Barcelona, Universitat Politècnica de Catalunya, Barcelona, Spain
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  • Ana I. Jiménez,

    1. Departamento de Química Orgánica, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), CSIC–Universidad de Zaragoza, Zaragoza, Spain
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  • Carlos Cativiela,

    1. Departamento de Química Orgánica, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), CSIC–Universidad de Zaragoza, Zaragoza, Spain
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  • Carlos Alemán

    Corresponding author
    1. Departament d'Enginyeria Química, E. T. S. d'Enginyeria Industrial de Barcelona, Universitat Politècnica de Catalunya, Barcelona, Spain
    2. Centre for Research in Nano-Engineering, Universitat Politècnica de Catalunya, Campus Sud, Edifici C', Barcelona, Spain
    • Correspondence to: Carlos Aleman, Departament d'Enginyeria Química, E. T. S. d'Enginyeria Industrial de Barcelona, Universitat Politècnica de Catalunya, Diagonal 647, Barcelona E-08028, Spain; e-mail: joan.torras@upc.edu and carlos.aleman@upc.edu

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  • This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

ABSTRACT

The conformational preferences of the N-acetyl-N′-methylamide derivatives of the four octahydroindole-2-carboxylic acid (Oic) stereoisomers have been investigated in the gas-phase and in aqueous solution using quantum mechanical calculations. In addition to the conformational effects provoked by the stereochemical diversity of Oic, which presents three chiral centers, results provide evidence of interesting and rather unusual features. The conformational preferences of the Oic stereoisomers in solution are only well described by applying a complete and systematic search process, results achieved by simple re-optimization of the gas-phase minima being very imprecise. This is because the conformational rigidity detected in the gas-phase, which is imposed by the chemical restrictions of the fused bicyclic skeleton, disappears in aqueous solution, the four stereoisomers behaving as flexible molecules in this environment. Thus, in general, the γ-turn is the only minimum energy conformation in the gas-phase while in aqueous solution the helical, polyproline-II and γ-turn motifs are energetically favored. Molecular dynamics simulations indicate that the conformational flexibility predicted by quantum mechanical calculations for the four Oic stereoisomers in solution is satisfactorily reproduced by classical force-fields. © 2014 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 102: 176–190, 2014.

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