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Investigating the inclusion properties of aromatic amino acids complexing beta-cyclodextrins in model peptides

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Abstract

Cyclodextrins are commonly used as complexing agents in biological, pharmaceutical, and industrial applications since they have an effect on protein thermal and proteolytic stability, refolding yields, solubility, and taste masking. β-cyclodextrins (β-CD), because of their cavity size are a perfectly suited complexing agent for many common guest moieties. In the case of peptide-cyclodextrin and protein-cyclodextrin host–guest complexes the aromatic amino acids are reported to be the principal responsible of the interaction. For these reasons, we have investigated the inclusion properties of nine designed tripeptides, obtained permuting the position of two l-alanines (Ala, A) with that of one l-tryptophan (Trp, W), l-phenylalanine (Phe, F), or l-tyrosine (Tyr, Y), respectively. Interestingly, the position of the aromatic side-chain in the sequence appears to modulate the β-CD:peptide binding constants, determined via UV–Vis and NMR spectroscopy, which in turn assumes values higher than those reported for the single amino acid. The tripeptides containing a tyrosine showed the highest binding constants, with the central position in the Ac-AYA-NH2 peptide becoming the most favorite for the interaction. A combined NMR and Molecular Docking approach permitted to build detailed complex models, highlighting the stabilizing interactions of the neighboring amino acids backbone atoms with the upper rim of the β-CD.

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Acknowledgments

The authors are grateful to Cristina Di Donato for useful discussion. This work was partially funded by M.I.U.R. Grants PRIN 2010 (to Roberto Fattorusso).

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The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Via A. Vivaldi 43, 81100, Caserta, Italy

    Jolanda Valentina Caso, Luigi Russo, Maddalena Palmieri, Gaetano Malgieri, Carla Isernia & Rosa Iacovino

  2. Department of Pharmacy, University of Naples Federico II, Via Mezzocannone 16, 80134, Naples, Italy

    Stefania Galdiero & Annarita Falanga

Authors
  1. Jolanda Valentina Caso
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  2. Luigi Russo
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  3. Maddalena Palmieri
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  4. Gaetano Malgieri
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  5. Stefania Galdiero
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  6. Annarita Falanga
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  7. Carla Isernia
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  8. Rosa Iacovino
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Corresponding author

Correspondence to Rosa Iacovino.

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Handling Editor: D. Tsikas.

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Caso, J.V., Russo, L., Palmieri, M. et al. Investigating the inclusion properties of aromatic amino acids complexing beta-cyclodextrins in model peptides. Amino Acids 47, 2215–2227 (2015). https://doi.org/10.1007/s00726-015-2003-4

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  • DOI: https://doi.org/10.1007/s00726-015-2003-4

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