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These properties are principally based on the binding and activation of antithrombin (AT) through the pentasaccharide sequence GlcNAc\/NS,6S\u2010GlcA\u2010GlcNS,3,6S\u2010IdoA2S\u2010GlcNS,6S (AGA*IA). Literature data show that the population of the <jats:sup>2<\/jats:sup><jats:italic>S<\/jats:italic><jats:sub>0<\/jats:sub> ring conformation of the 2\u2010<jats:italic>O<\/jats:italic>\u2010sulfo\u2010\u03b1\u2010<jats:sc>l<\/jats:sc>\u2010iduronic acid (IdoA2S) motif correlates with the affinity and activation of AT. It was recently demonstrated that two synthetic AGA*IA\u2010containing hexasaccharides (one G unit added at the reducing end), differing in the degree of sulfation of the IdoA unit, show comparable affinity and ability to activate AT, despite a different conformation of the IdoA residue. In this paper, the binding of these two glycans to AT was studied by isothermal titration microcalorimetry (ITC), transferred (tr\u2010) NOESY, saturation transfer difference (STD) NMR spectroscopy and molecular dynamics (MD) simulations. Results indicated that both the IdoA2S and the IdoA units assume a <jats:sup>2<\/jats:sup><jats:italic>S<\/jats:italic><jats:sub>0<\/jats:sub> conformation when bound with AT, and so present a common binding epitope for the two glycans, centred on the AGA*IA sequence.<\/jats:p>","DOI":"10.1002\/cbic.201800095","type":"journal-article","created":{"date-parts":[[2018,3,24]],"date-time":"2018-03-24T19:53:03Z","timestamp":1521921183000},"page":"1178-1188","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Recognition and Conformational Properties of an Alternative Antithrombin Binding Sequence Obtained by Chemoenzymatic Synthesis"],"prefix":"10.1002","volume":"19","author":[{"given":"Eduardo","family":"Stancanelli","sequence":"first","affiliation":[{"name":"Department NMR and Carbohydrates Istituto di Ricerche Chimiche e Biochimiche \u201cG. Ronzoni\u201d  via G. Colombo 81 20133 Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Elli","sequence":"additional","affiliation":[{"name":"Department NMR and Carbohydrates Istituto di Ricerche Chimiche e Biochimiche \u201cG. Ronzoni\u201d  via G. Colombo 81 20133 Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po\u2010Hung","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Division of Chemical Biology and Medicinal Chemistry Eshelman School of Pharmacy University of North Carolina  Chapel Hill NC 27599 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Chemical Biology and Medicinal Chemistry Eshelman School of Pharmacy University of North Carolina  Chapel Hill NC 27599 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7246-9113","authenticated-orcid":false,"given":"Marco","family":"Guerrini","sequence":"additional","affiliation":[{"name":"Department NMR and Carbohydrates Istituto di Ricerche Chimiche e Biochimiche \u201cG. Ronzoni\u201d  via G. 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