Unique Extracellular Matrix Heparan Sulfate from the Bivalve Nodipecten nodosus (Linnaeus, 1758) Safely Inhibits Arterial Thrombosis after Photochemically Induced Endothelial Lesion

NMR structural determination of unique invertebrate glycosaminoglycans endowed with medical properties

“…1,2 Interestingly, recent NMR structural analyses on the HS extracted from the marine bivalve mollusk N. nodosus have demonstrated a very unique GAG in terms of sulfation pattern and the rational bases of the HS biosynthetic routes. 22 This novel GAG was observed to be composed of a high degree of a-D-GlcNAc residues, a lack of a-L-IdoA residues, and the occurrence of the rarest 2-and 3-sulfation at a-D-GlcA units (Fig. 7A).…”

“…These characteristics are very uncommon in mammalian HSs or mollusk heparinoids studied up to that time. 22 Interpretation about how we have reached conclusions about this rare HS from the marine bivalve through the use of NMR is given below.…”

“…22 It was shown that the mollusk HS has an ATdependent anticoagulant activity with potentiality fivefold lower than the standard porcine Hp as monitored by the aPTT method. 22 Recently The same group has also recently studied the medical potentials of the bivalve GAG in what concerns its beneficial application in P-selectin and heparanase activities seen in cancer and inflammation events. 76 …”

“…Therapeutic GAGs from invertebrates, from terrestrial or marine habitat, are also available and have shown curiously different structures as compared to the mammalian standards. Among numerous invertebrate GAGs that have been studied so far in terms of both structure and function, representative examples are the holothurian fucosylated chondroitin sulfate (FucCS), 14,15 the acharan sulfate (AS) from the giant African snail Achatina fulica, 16e18 the ascidian DSs of unique sulfation patterns, 19e21 the novel HS from the bivalve Nodipecten nodosus, 22 and the hybrid HS/Hp found in the head of the shrimp Litopenaeus vannamei. 23 Like in structural analyses of mammalian GAGs, solution nuclear magnetic resonance (NMR) spectroscopy alone or combined with other techniques, has been the preferred method used in structural characterization of the invertebrate molecules.…”

Unravelling Glycobiology by NMR Spectroscopy

“…This can be exemplified with the 1D spectrum of GlcNS at Figure 6A. The 1 H-peaks can be assigned through spin-systems from TOCSY spectrum using this same hydrated low-temperature condition ( Figure 7A The HS in panel A was from cultures of chinese hamster ovarian (CHO) cells [10], the UFH in panel B was from a pharmaceutical supplier, and the HS in panel C was extracted from the bivalve Nodipecten nodosus [16]. Note that the (B) UFH and (C) HS have respectively low and high amounts of glucuronic acids (GlcUA), as demonstrated by the tiny or missing color-coded peaks in their respective 13 C-HSQC spectra of panels D and E. In these panels, the letters used are A for glucosamine, I for iduronic acid, G for glucuronic acid, NAc for N-acetyl, NS for N-sulfation, 6X for 6-(un)substituted, 2S for 2-sulfation, XS for 2-and/or 3-sulfation, and 3S for 3-sulfation.…”