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Inter- versus intra-molecular cyclization of tripeptides containing tetrahydrofuran amino acids: a density functional theory study on kinetic control

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Abstract

Density functional B3LYP method was used to investigate the preference of intra- and inter-molecular cyclizations of linear tripeptides containing tetrahydrofuran amino acids. Two distinct model pathways were conceived for the cyclization reaction, and all possible transition states and intermediates were located. Analysis of the energetics indicate intermolecular cyclization being favored by both thermodynamic and kinetic control. Geometric and NBO analyses were performed to explain the trends obtained along both the reaction pathways. Conceptual density functional theory-based reactive indices also show that reaction pathways leading to intermolecular cyclization of the tripeptides are relatively more facile compared to intramolecular cyclization.

DFT- and NBO-based analysis of intra- and inter-molecular cyclizations of linear tripeptides containing tetrahydrofuran amino acids show the intermolecular path as favored by both thermodynamic and kinetic control

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Acknowledgment

We thank the Department of Science and Technology, New Delhi, Government of India for financial support (SR/S1/OC01/2007).

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  1. Center for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology, Hyderabad, 500 032, India

    N. V. Suresh Kumar, U. Deva Priyakumar & Harjinder Singh

  2. Central Drug Research Institute, CSIR, Lucknow, 226 001, India

    Saumya Roy & Tushar Kanti Chakraborty

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  1. N. V. Suresh Kumar
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Correspondence to Harjinder Singh.

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Kumar, N.V.S., Priyakumar, U.D., Singh, H. et al. Inter- versus intra-molecular cyclization of tripeptides containing tetrahydrofuran amino acids: a density functional theory study on kinetic control. J Mol Model 18, 3181–3197 (2012). https://doi.org/10.1007/s00894-011-1326-7

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