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Conformational preferences of Ac-Pro-azaXaa-NHMe (Xaa = Asn, Asp, Ala) and the effect of intramolecular hydrogen bonds on their stability in gas phase and solution

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Abstract

The conformational preferences of three azadipeptides Ac-Pro-azaXaa-NHMe [Xaa = Asn (1), Asp (2), Ala (3)] have been carried out in gas phase and solution (water) using the density functional method B3LYP/6–311 +  + G(d,p) to explore the effect of the change of side chain of azaamino acids at the i + 2 position on the stability of these components. The most stable conformations of compounds (1), (2), and (3) have an amid bond oriented trans, trans, and cis, respectively, in gas phase, whereas the orientation of amid bond in water solvent of compounds (2) and (3) has changed to cis and trans, respectively. We have also noticed the importance of backbone-side chain hydrogen bonds in the stabilization of the β turn motif in gas phase since this motif is more stable in the case of compounds (1) and (2) and less stable in the case of compound (3) in which these hydrogen bonds are absent. Furthermore, the βII(βII′) turn structure is more stable than βI turn for all conformations of the three compounds in gas phase, while it is not true in the case of some conformations in solution. Moreover, the stability of β turn increases from azaAsn to azaAsp which could be due to the side chain’s basic nature of azaAsn. In general, hydrogen bonds were found to play a key role in the stabilization of these compounds since most of conformers are lower in energy when they have more than two hydrogen bond interactions while conformations with one or no hydrogen bonds are higher in energy and thus less stable.

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Authors and Affiliations

  1. LIMAS, Faculty of Sciences Dhar El Mahraz, University Sidi Mohamed Ben Abdallah, Fez, Morocco

    Mouna El Khabchi, Hiba Lahlou, Zineb El Adnani, Mohammed Mcharfi, Mohammed Benzakour, Asmae Fitri & Adil Touimi Benjelloun

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  1. Mouna El Khabchi
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  2. Hiba Lahlou
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  3. Zineb El Adnani
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  4. Mohammed Mcharfi
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  5. Mohammed Benzakour
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Contributions

MEK: performed the calculations, contributed to the interpretation of the results, and wrote the manuscript. HL and ZEA: contributed to the interpretation of the results. MM and MB: supervised the findings of this work, contributed to the interpretation of the results, and were in charge of overall direction and planning. AF and ATB: contributed to the final version of the manuscript.

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Correspondence to Mouna El Khabchi.

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El Khabchi, M., Lahlou, H., El Adnani, Z. et al. Conformational preferences of Ac-Pro-azaXaa-NHMe (Xaa = Asn, Asp, Ala) and the effect of intramolecular hydrogen bonds on their stability in gas phase and solution. J Mol Model 27, 368 (2021). https://doi.org/10.1007/s00894-021-04992-x

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  • DOI: https://doi.org/10.1007/s00894-021-04992-x

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