Dynamic properties of biologically active synthetic heparin-like hexasaccharides

Angulo, Jesús, Hricovíni, Milo, Gairi, Margarida, Guerrini, Marco, de Paz, José Luis, Ojeda, Rafael, Martín-Lomas, Manuel and Nieto, Pedro M. (2005) Dynamic properties of biologically active synthetic heparin-like hexasaccharides. Glycobiology, 15 (10). pp. 1008-1015. ISSN 0959-6658

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Abstract

A complete study of the dynamics of two synthetic heparin-like hexasaccharides, D-GlcNHSO3-6-SO4-α-(1→4)-L-IdoA-2-SO4-α-(1→4)-D-GlcNHSO3-6-SO4-α-(1→4)-L-IdoA-2-SO4-α-(1→4)-D-GlcNHSO3-6-SO4-α-(1→4)-L-IdoA-2-SO4-α-1→iPr (1) and →4)-L-IdoA-2-SO4-α-(1→4)-D-GlcNHAc-6-SO4-α-(1→4)-L-IdoA-α-(1→4)-D-GlcNHSO3-α-(1→4)-L-IdoA-2-SO4-α-1→iPr (2), has been performed using 13C-nuclear magnetic resonance (NMR) relaxation parameters, T1, T2, and heteronuclear nuclear Overhauser effect (NOEs). Compound 1 is constituted from sequences corresponding to the major polysaccharide heparin region, while compound 2 contains a sequence never found in natural heparin. They differ from each other only in sulphation patterns, and are capable of stimulating fibroblast growth factors (FGFs)-1 induced mitogenesis. Both oligosaccharides exhibit a remarkable anisotropic overall motion in solution as revealed by their anisotropic ratios (τ /τ||), 4.0 and 3.0 respectively. This is a characteristic behaviour of natural glycosaminoglycans (GAG) which has also been observed for the antithrombin (AT) binding pentasaccharide D-GlcNHSO3-6-SO4-α-(1→4)-D-GlcA-β-(1→4)-D-GlcNHSO3-(3,6-SO4)-α-(1→4)-L-IdoA-2-SO4-α-(1→4)-D-GlcNHSO3-6-SO4-α-1→Me (3) (Hricovíni, M., Guerrini, M., Torri, G., Piani, S., and Ungarelli, F. (1995) Conformational analysis of heparin epoxide in aqueous solution. An NMR relaxation study. Carbohydr. Res., 277, 11–23). The motional properties observed for 1 and 2 provide additional support to the suitability of these compounds as heparin models in agreement with previous structural (de Paz, J.L., Angulo, J., Lassaletta, J.M., Nieto, P.M., Redondo-Horcajo, M., Lozano, R.M., Jiménez-Gallego, G., and Martín-Lomas, M. (2001) The activation of fibroblast growth factors by heparin: synthesis, structure and biological activity of heparin-like oligosaccharides. Chembiochem, 2, 673–685; Ojeda, R., Angulo, J., Nieto, P.M., and Martin-Lomas. M. (2002) The activation of fibroblast growth factors by heparin: synthesis and structural study of rationally modified heparin-like oligosaccharides. Can. J. Chem,. 80, 917–936; Lucas, R., Angulo, J., Nieto, P.M., and Martin-Lomas, M. (2003) Synthesis and structural studies of two new heparin-like hexasaccharides. Org. Biomol. Chem., 1, 2253–2266) and biological data (Angulo, J., Ojeda, R., de Paz, J.L., Lucas, R., Nieto, P.M., Lozano, R.M., Redondo-Horcajo, M., Giménez-Gallego, G., and Martín-Lomas, M. (2004) The activation of fibroblast growth factors (FGFs) by glycosaminoglycans: influence of the sulphation pattern on the biological activity of FGF-1. Chembiochem, 5, 55–61). Fast internal motions observed for the less sulphated compound 2, as compared with 1, may be related to their different behavior in stimulating FGF1-induced mitogenic activity.

Item Type: Article
Uncontrolled Keywords: anistropy,fgf interaction,heparan sulphate,heparin,nmr relaxation
Faculty \ School: Faculty of Science > School of Pharmacy
Related URLs:
Depositing User: Pure Connector
Date Deposited: 21 Oct 2013 20:08
Last Modified: 31 Oct 2019 14:14
URI: https://ueaeprints.uea.ac.uk/id/eprint/43751
DOI: 10.1093/glycob/cwi091

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