title: Investigating the inclusion properties of aromatic amino acids complexing beta-cyclodextrins in model peptides.
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.
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Via A. Vivaldi 43, 81100, Caserta, Italy.
authors.forename: Jolanda Valentina
authors.initials: JV
authors.lastname: Caso
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Via A. Vivaldi 43, 81100, Caserta, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Russo
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Via A. Vivaldi 43, 81100, Caserta, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Palmieri
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Via A. Vivaldi 43, 81100, Caserta, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Malgieri
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via Mezzocannone 16, 80134, Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Galdiero
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via Mezzocannone 16, 80134, Naples, Italy.
authors.forename: Annarita
authors.initials: A
authors.lastname: Falanga
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Via A. Vivaldi 43, 81100, Caserta, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Isernia
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Via A. Vivaldi 43, 81100, Caserta, Italy. rosa.iacovino@unina2.it.
authors.forename: Rosa
authors.initials: R
authors.lastname: Iacovino
mesh_terms: D024322:Amino Acids, Aromatic / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D002479:Inclusion Bodies; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D024322:Amino Acids, Aromatic; D010446:Peptide Fragments; D047392:beta-Cyclodextrins
keywords: Aromatic amino acids; Inclusion complex; Molecular docking; NMR; UV–Vis spectroscopy; β-Cyclodextrin