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A Rapid and Mild Sulfation Strategy Reveals Conformational Preferences in Therapeutically Relevant Sulfated Xylooligosaccharides
Author(s) -
Vo Yen,
Schwartz Brett D.,
Onagi Hideki,
Ward Jas S.,
Gardiner Michael G.,
Banwell Martin G.,
Nelms Keats,
Malins Lara R.
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202100527
Subject(s) - sulfation , chemistry , pyridinium , monosaccharide , homogeneous , reagent , glycosaminoglycan , biochemistry , combinatorial chemistry , organic chemistry , physics , thermodynamics
Although sulfated xylooligosaccharides are promising therapeutic leads for a multitude of afflictions, the structural complexity and heterogeneity of commercially deployed forms (e. g. Pentosan polysulfate 1 ) complicates their path to further clinical development. We describe herein the synthesis of the largest homogeneous persulfated xylooligomers prepared to date, comprising up to eight xylose residues, as standards for biological studies. Near quantitative sulfation was accomplished using a remarkably mild and operationally simple protocol which avoids the need for high temperatures and a large excess of the sulfating reagent. Moreover, the sulfated xylooligomer standards so obtained enabled definitive identification of a pyridinium contaminant in a sample of a commercially prepared Pentosan drug and provided significant insights into the conformational preferences of the constituent persulfated monosaccharide residues. As the spatial distribution of sulfates is a key determinant of the binding of sulfated oligosaccharides to endogenous targets, these findings have broad implications for the advancement of Pentosan‐based treatments.