Investigating the relationship between temperature, conformation and calcium binding in heparin model oligosaccharides

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Hughes, Ashley
Meneghetti, Maria [UNIFESP]
Huang, Teng-Yi
Hung, Shang-Cheng
Elli, Stefano
Guerrini, Marco
Rudd, Timothy
Lima, Marcelo [UNIFESP]
Yates, Edwin [UNIFESP]
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Glycosaminoglycans such as heparan sulfate (HS) are major components of the cell surface and extra cellular matrix (ECM) of all multicellular animals, connecting cells to each other as well as to their environment. The ECM must, therefore, both sense and accommodate changes to external conditions. Heparin, a model compound for HS, responds to increased temperatures, involving changes in the populations of conformational states with implications for the binding of HS to proteins, cations and, potentially, for its activity. A fully(13)C and N-15 labelled model octasasccharide
D-G1cNS6S alpha(1-4) L-IdoA2S [alpha(1-4) D-G1cNS6S alpha(1-4) L-IdoA2S](2) alpha(1-4) D-G1cNS6S alpha(1-4) L-IdoA1,6an, was studied by H-1, C-13 and N-15 NMR, revealing complex changes in chemical shifts and conformation, over temperatures (280 - 305 K), comfortably within the range relevant to terrestrial biology. These complex conformational changes indicated an interaction between the carboxylate group of L-iduronate and D-glucosamine residues that was susceptible to temperature changes in this range, while the well-documented hydrogen bond between the N-sulfamido group of glucosamine and the hydroxyl group at position-3 of iduronate remained intact. Unexpectedly, despite the presence of similar thermally-induced conformational changes in a heparin octasaccharide fraction in the sodium ion form, its subsequent binding to calcium ions and their resulting conformation was stringently maintained, as judged by comparisons of H-1 NMR chemical shifts. (C) 2016 Published by Elsevier Ltd.
Carbohydrate Research. Oxford, v. 438, p. 58-64, 2017.