| Abstract | Recently, a new heparin disaccharide-binding site on the convex side of cobra cardiotoxin (CTX) was identified by NMR spectroscopy and molecular modeling. To further characterize this site two heparin-like disaccharides were synthesized for binding studies with CTX, and a trisaccharide was synthesized for testing the sequence of the disaccharide binding to CTX. Thus six differentially protected monosaccharide building blocks (three l-iduronic acids and three d-glucosamines) were prepared. These include a l-iduronic acid elongation building block namely methyl 2-O-acetyl-4-O-levulinoyl-3-O-pivaloyl-[alpha]-l-idopyranosyluronate trichloroacetimidate for which a single-crystal X-ray structure was determined to have Mr?=?576.79, a?=?9.3098(11)?A [alpha]?=?90?, b?=?10.3967(12)?A [beta]?=?90?, c?=?28.026(3)?A [gamma]?=?90?, V?=?2712.7(6)?A3, P212121, Z?=?4, [mu]?=?0.71073?A, and R?=?0.0378 for 7586 observed reflections. It shows that the molecular structure of the donor is in the 1C4 conformation with significant 1,3-diaxial interactions between O-1 and O-3 as well as O-2 and O-4. The disaccharides and trisaccharide vary in the degree and position of O- and N-sulfation. The pivaloyl group was used as permanent protecting group of hydroxyl. The levulinoyl group was used as the temporary protecting group to protect the hydroxyl for elongation. |
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