Fig. 1.

Simplified formula of a representative ATBR-containing chain of porcine mucosal heparin (a) and the corresponding glycol-split derivative (b) obtained by periodate oxidation and borohydride reduction of nonsulfated glucuronic (G/G′) and iduronic (I) residues, to generate gsG/gsG′, and gsI [13]

LR = linkage region [23] at the “reducing” end (RE). The biochemical formula of ATBR is indicated in structure (a), starting with a residue I that is not part of the pentasaccharidic active site, but most often precedes it. Structure (a) is adapted from [22]; a major modification involves the A_NS,6S residue at the non-reducing end (NRE), assumed to be the consequence of cleavage (by an endo-β-D-glucosidase) of a G-A_NS6S glycosidic bond in the chains of the heparin proteoglycan precursor (“macromolecular heparin”). The structure of the “full” linkage region LR is reported in (c) and (d) for heparin and RO-heparin, respectively, where G_LR is the G residue in the LR, Gal1 and Gal2 are two galactose residues, Xyl is xylose, Ser is serine [23]. The two glycol-split residues (gsG_LR and gsXyl) in the LR of gs-heparin were not previously described (see text). Circled residues in the unmodified heparin structure (a) and (c) highlight unsubstituted diol groups susceptible of glycol-splitting