Efficient Synthesis of Glycosaminoglycan Analogs

Abstract

Glycosaminoglycans (GAGs) are among the most complex, biologically active polysaccharides in nature. The complexity of GAGs greatly impedes their synthesis, thus complicating the structure-property studies that are so necessary for us to understand the roles of GAGs in natural processes, in pathogen invasion, and to understand how to develop effective interventions, for example, to prevent undesired GAG hijacking by pathogens. Total synthesis of GAG oligomers from monosaccharide building blocks is useful, but incredibly labor-intensive, expensive, and inefficient. In this study, we report a regiospecific synthetic route to two types of designed GAG analogs by chemical modification of commercially available, inexpensive cellulose acetate. Cellulose acetate was first brominated, followed by azide displacement to introduce azides as the GAG amine precursors. The resulting 6-N cellulose acetate was then saponified to liberate 6-OH groups. Subsequent oxidation of the liberated primary hydroxyl groups to carboxyl groups was smoothly effected by a TEMPO-catalyzed process. Finally, the azides were reduced to amines using an aqueous process, new to polysaccharide chemistry, employing reduction by dithiothreitol (DTT). Alternatively, another process new to polysaccharide chemistry could be employed to convert most of the azides to acetamido groups (mimicking those present, for example, in native hyaluronic acid) by reduction with thioacetic acid. All the intermediates and products were characterized by H NMR,C NMR, and FT-IR spectroscopy. This synthetic route provides access to GAG analogs that will be of great interest for exploring structure-property relationships in various biomedical applications.

Regioselective Bromination of the Dextran Nonreducing End Creates a Pathway to Dextran-Based Block Copolymers

“…Our first task was to confirm our hypothesis that this single, terminal primary alcohol, chemically distinct from other hydroxyl groups along the chain, could be cleanly converted to 6-Br by Furuhata bromination (Scheme ). We selected reaction conditions similar to those in previous work used to prepare brush-like structures from cellulose and other polysaccharides, employing NBS as the bromination reagent and PPh 3 as the promoter in DMSO solvent. ,, Given the extremely low concentration of primary alcohols, 100 equiv each of NBS and PPh 3 were added to increase the likelihood of collisions leading to desired reactions. The reaction product was purified by dialysis against water and collected by freeze-drying.…”

A graph neural network model to estimate cell-wise metabolic flux using single cell RNA-seq data

“…An essential part of metabolic map is the biosynthesis pathways. KEGG database and literature (Moffatt and Ashihara 2002; DeAngelis et al 2013; Zhang et al 2015a; Zhang et al 2015b; Krasnova and Wong 2016; Zulueta et al 2016; Lv et al 2017; Sun et al 2018; Gao and Edgar 2019; Sun et al 2020a; Sun et al 2020b) are the main information sources used for building biosynthesis modules. We collected 69 biosynthesis modules forming 10 super modules, namely biosynthesis of hyaluronic acid, glycogen, glycosaminoglycan, N-linked glycan, O-linked glycan, sialic acid, glycan, purine, pyrimidine, and steroid hormones.…”

“…An essential part of metabolic map is the biosynthesis pathways. KEGG database and literature [7,[55][56][57][58][59][60][61][62][63][64] are the main information sources used for building biosynthesis modules. We collected 69 biosynthesis modules forming 9 super modules, namely biosynthesis of hyaluronic acid, glycogen, glycosaminoglycan, N-linked glycan, O-linked glycan, Sialic acid, Glycan, Purine and Pyrimidine.…”

Antibacterial modification of Lyocell fiber: A review

“…Oxidation of cellulose is one way to impart reactivity and create handles for appending antibacterials to Lyocell fibers using more facile chemistries. Primary cellulose hydroxyls can be oxidized to carboxyl groups (De Nooy, Besemer, & Vanbekkum, 1995;Gao & Edgar, 2019;Saito, Kimura, Nishiyama, & Isogai, 2007), which can be sites for attachment by, e.g., ester, amide, or hydrazide linkages. Periodate oxidation of the vicinal 2, 3-diol of cellulose affords ring-opened monosaccharides within the chain, that possess now 2, 3-dialdehyde moieties.…”