title: Binding and stabilisation effects of glycodendritic compounds with peanut agglutinin.
abstract: A number of new polyhydroxy-dendritic structures have been constructed from a few basic modules. The cores were derived from N-tert(butyloxycarbonyl)tris[(propargyloxy)methyl]aminomethane, N,N'-bis-1,3-(tris-(propargyloxymethyl)methyl)-5-(hydroxymethyl)isophthalamide, and N,N',N″-tris-1,3,5-(tris-(propargyloxymethyl)methyl)-1,3,5-benzene tricarboxamide while the terminal groups were derived from β-azido-galactose and β-azido-lactose leading to six new glycodendrimeric compounds with up to 63 hydroxyl groups on the periphery. The binding ability of the new compounds to peanut agglutinin (PNA), a galactose recognizing lectin from Arachis hypogaea, was investigated by nano-Isothermal Titration Calorimetry and nano-Differential Scanning Calorimetry. We found that the compounds had stronger stabilising effect on the macromolecules compared to the corresponding sugars. The interaction between lectin and the glycodendrimeric unit is entropically driven with only a low enthalpic contribution. A trend was found with increasing number of carbohydrates that is strongly influenced by the steric constraints of the ligands. Our results indicate the significance of multivalency and size control in the successful design of lectin inhibitors.
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48. Vas. Constantinou Ave., 11635 Athens, Greece.
authors.forename: Mazen Haj
authors.initials: MH
authors.lastname: Sleiman
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48. Vas. Constantinou Ave., 11635 Athens, Greece.
authors.forename: Róbert
authors.initials: R
authors.lastname: Csonka
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48. Vas. Constantinou Ave., 11635 Athens, Greece.
authors.forename: Cécile
authors.initials: C
authors.lastname: Arbez-Gindre
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48. Vas. Constantinou Ave., 11635 Athens, Greece.
authors.forename: Georgios A
authors.initials: GA
authors.lastname: Heropoulos
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48. Vas. Constantinou Ave., 11635 Athens, Greece.
authors.forename: Theodora
authors.initials: T
authors.lastname: Calogeropoulou
authors.affiliation: Department of Food, Environmental and Nutritional Sciences (DeFENS), Università degli Studi di Milano, Via Celoria 2, 20133 Milano, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Signorelli
authors.affiliation: Department of Food, Environmental and Nutritional Sciences (DeFENS), Università degli Studi di Milano, Via Celoria 2, 20133 Milano, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Schiraldi
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48. Vas. Constantinou Ave., 11635 Athens, Greece.
authors.forename: Barry R
authors.initials: BR
authors.lastname: Steele
authors.affiliation: Department of Food, Environmental and Nutritional Sciences (DeFENS), Università degli Studi di Milano, Via Celoria 2, 20133 Milano, Italy. Electronic address: dimitrios.fessas@unimi.it.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Fessas
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48. Vas. Constantinou Ave., 11635 Athens, Greece. Electronic address: mskreta@eie.gr.
authors.forename: Maria
authors.initials: M
authors.lastname: Micha-Screttas
mesh_terms: D002151:Calorimetry; D002241:Carbohydrates / Q000737:chemistry; D005690:Galactose / Q000737:chemistry* / Q000378:metabolism; D007785:Lactose / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D019887:Peanut Agglutinin / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D013816:Thermodynamics
chemical_list: D002241:Carbohydrates; D019887:Peanut Agglutinin; D007785:Lactose; D005690:Galactose
keywords: Arachis hypogaea; Calorimetry; DSC; Glycodendrimer; ITC; Lectin; Multivalency; PNA