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Theoretical conformational analysis of opiate peptides Leu-Enkephalin (H-Tyr-Gly-Gly-Phe-Leu-OH) and its two thioamide analogs (H-Tyr-Glyψ[CSNH]Gly-Phe-Leu-OH) and (H-Tyr-Gly-Glyψ[CSNH]Phe-Leu-OH)

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Abstract

In order to find informations on the native structure of the Leu-Enkephalin opiate peptide, the parent peptide and its two thioamide analogs (Thio-Gly2)Leu-Enkephalin and (Thio-Gly3)Leu-Enkephalin were studied by the theoretical method PEPSEA. This comparative conformational analysis showed that the active conformation is a β turn structure centered on Gly3 and Phe4. Moreover, this study showed also that the more active analog (Thio-Gly2)Leu-Enk has a lower tendency to adopt this structure. Consequently, its high activity can only be explained by its long lifetime due to its resistance to enzymatic hydrolysis, following the substitution of the amide linkage by the thioamide one. The weakly active analog (Thio-Gly3)Leu-Enk does not adopt this structure and prefers instead a β turn structure centered on Gly2 and Gly3. This study also confirmed the importance of the distances between the Tyr and Phe residues at positions 1 and 4, and that of the terminal Tyrosine N-H group which must be free of any intramolecular hydrogen bond in order to be available in the molecular recognition process.

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Authors and Affiliations

  1. Laboratoire de Chimie Appliquée, Département de Chimie, Faculté des Sciences et Techniques, Université Sidi Mohamed Ben Abdellah, BP 2202, Fes, Morocco

    Chakib Ameziane Hassani & Mourad Houssat

  2. Laboratoire de Génie Mécanique, Faculté des Sciences et Techniques, Université Sidi Mohamed Ben Abdellah, BP 2202, Fes, Morocco

    Jamal Eddine Hazm

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  1. Chakib Ameziane Hassani
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  2. Mourad Houssat
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  3. Jamal Eddine Hazm
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Correspondence to Chakib Ameziane Hassani.

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Ameziane Hassani, C., Houssat, M. & Hazm, J.E. Theoretical conformational analysis of opiate peptides Leu-Enkephalin (H-Tyr-Gly-Gly-Phe-Leu-OH) and its two thioamide analogs (H-Tyr-Glyψ[CSNH]Gly-Phe-Leu-OH) and (H-Tyr-Gly-Glyψ[CSNH]Phe-Leu-OH). Struct Chem 29, 481–489 (2018). https://doi.org/10.1007/s11224-017-1045-5

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