Preparation of Possible P Selectin Inhibitor from Bovine Thyroglobulin, (Di-hydrido) Sulfo Hydrate 1, 5 Anhydro L-fucitol

Jesus Christus,Michael Arden Madson

doi:10.11648/j.wjfst.20210501.12

Abstract

P selectin is known to mediate several disease states through the binding of epitopes on the surface of endothelial cells. These diseases include cancer, cancer metastasis and inflammation. Sulfo Lewis a is a sulfated oligosaccharide could bind P selectin. A possible novel inhibitor of P-selectin binding may attenuate these diseases. One possible inhibitor is prepared from bovine thyroglobulin in one step, with appropriate work-up, from a readily abundant source, bovine thyroid gland, via novel chemistry. That molecule is (di-hydrido) sulfo hydrate 1, 5 anhydro L-fucitol. This chemistry is known to occur for the preparation of 1, 5 anhydro oligosaccharides from K casein and bovine milk. Another example of this chemistry has also been prepared; the di-(hydrido) di-phosphate di-hydrate 2, 5 anhydro mannitol (glucitol) from an ethanol extract of banana fruit. The molecule, here, would be the first report of H<sup>-</sup> nucleophile attack of a non-phosphorylated glycoside. In addition to components of the O-linked oligosaccharide, to originate from bovine thyroglobulin requiring a tyrosine sulfate for binding. This work provides methods for preparing (di-hydrido) sulfo 1, 5 anhydro L-fucitol, as a possible inhibitor of P-selectin binding, in addition to those reported. These include; the di (di-hydrido) trisaccharide di-(hydrido) di-phosphate di-hydrate serinyl (di-hydrido) sulfo tyrosine dipeptide as well as the tri (di-hydrido) sulfo tri-hydrate 1, 5 anhydro trisaccharide alditol. Both of the latter two originate from bovine thyroglobulin and have been or will, possibly, be reported.

Highlights

Pselectin is involved in several disease states, thrombosis, cancer, cancer metastasis and inflammation [1], Sulfo lewis a is known to bind P selectin [2]
The molecular components found to be derived from the O-linked oligosaccharide from bovine thyroglobulin, after treatment with NaBH4 in NH4OH is thought to be contain L-fucose, DN-acetyl glucosamine and glucose substituted with derivatized sulfate linked to derivatized di-phospho serinyl derivatized sulfo tyrosine dipeptide and the corresponding 1, 5 anhydro alditol trisaccharide tri-(di-hydrido) sulfate [3,4]
The pH drop is possibly due to the evolution of NH3 (g) during the reaction. This drop in pH prevents the ionization of the hydrated di-(hydrido) diphospho group at the anomeric center of the ‘reducing’ monosaccharide component of the total molecule cleaved out from bovine thyroglobulin

Summary

Introduction

Pselectin is involved in several disease states, thrombosis, cancer, cancer metastasis and inflammation [1], Sulfo lewis a is known to bind P selectin [2]. These authors have synthesized sulfated neoglycopolymers as selective inhibitors, mimics for binding epitopes to study this binding [2]. This monosaccharides are similar in structure to sulfo lewis a and because of the simplicity of the chemistry and work-up, the source is readily available the testing of these molecules for P-selectin inhibitors, would be reasonable. A simple method for testing the inhibition of binding of the sulfo lewis a epitope by these three molecules can be done with the use of recently reported carbohydrate affinity columns. [6]

Materials and Methods

Results and Discussion

Conclusions