Journal of Molecular Modeling

, Volume 18, Issue 7, pp 3181–3197 | Cite as

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

  • N. V. Suresh Kumar
  • U. Deva Priyakumar
  • Harjinder SinghEmail author
  • Saumya Roy
  • Tushar Kanti Chakraborty
Original Paper


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


Peptides Cyclization Planarity DFT NBO 



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

Supplementary material

894_2011_1326_MOESM1_ESM.pdf (838 kb)
ESM 1 (PDF 837 kb)


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • N. V. Suresh Kumar
    • 1
  • U. Deva Priyakumar
    • 1
  • Harjinder Singh
    • 1
    Email author
  • Saumya Roy
    • 2
  • Tushar Kanti Chakraborty
    • 2
  1. 1.Center for Computational Natural Sciences and BioinformaticsInternational Institute of Information TechnologyHyderabadIndia
  2. 2.Central Drug Research Institute, CSIRLucknowIndia

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