| 1. |
- Bouyoucef, S E, et al.
(author)
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Poster Session 2 : Monday 4 May 2015, 08
- 2015
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In: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
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Journal article (peer-reviewed)
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| 2. |
- Ferreira, Mjv, et al.
(author)
-
Poster Session 3 : Tuesday 5 May 2015, 08
- 2015
-
In: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
-
Journal article (peer-reviewed)
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| 3. |
- Hughes, Ashley J, 1987, et al.
(author)
-
Investigating the relationship between temperature, conformation and calcium binding in heparin model oligosaccharides
- 2017
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In: Carbohydrate Research. - : Elsevier BV. - 0008-6215. ; 438, s. 58-64
-
Journal article (peer-reviewed)abstract
- 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.
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| 4. |
- Meneghetti, M. C. Z., et al.
(author)
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Heparan sulfate and heparin interactions with proteins
- 2015
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In: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5689 .- 1742-5662. ; 12:110
-
Journal article (peer-reviewed)abstract
- Heparan sulfate (HS) polysaccharides are ubiquitous components of the cell surface and extracellular matrix of all multicellular animals, whereas heparin is present within mast cells and can be viewed as a more sulfated, tissue-specific, HS variant. HS and heparin regulate biological processes through interactions with a large repertoire of proteins. Owing to these interactions and diverse effects observed during in vitro, ex vivo and in vivo experiments, manifold biological/pharmacological activities have been attributed to them. The properties that have been thought to bestow protein binding and biological activity upon HS and heparin vary from high levels of sequence specificity to a dependence on charge. In contrast to these opposing opinions, we will argue that the evidence supports both a level of redundancy and a degree of selectivity in the structure-activity relationship. The relationship between this apparent redundancy, the multi-dentate nature of heparin and HS polysaccharide chains, their involvement in protein networks and the multiple binding sites on proteins, each possessing different properties, will also be considered. Finally, the role of cations in modulating HS/heparin activity will be reviewed and some of the implications for structure-activity relationships and regulation will be discussed.
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