Chemical Synthesis of Glycosaminoglycans

Abstract

Glycosaminoglycans (GAGs) as one major part of the glycocalyx are involved in many essential biological cell processes, as well as in many courses of diseases. Because of the potential therapeutic application of GAG polymers, fragments, and also derivatives toward different diseases (e.g., heparin derivatives against Alzheimer's disease), there is a continual growing demand for new chemical syntheses, which suffice the high claim to stereoselectivity and chemoselectivity. This Review summarizes the progress of chemical syntheses of GAGs over the last 10 years. For each class of the glycosaminoglycans-hyaluronan (HA), heparan sulfate/heparin (HS/HP), chondroitin/dermatan sulfate (CS/DS), and keratan sulfate (KS)-mainly novel glycosylation strategies, elongation sequences, and protecting group patterns are discussed, but also (semi)automated syntheses, enzymatic approaches, and functionalizations of synthesized or isolated GAGs are considered.

A microbial–enzymatic strategy for producing chondroitin sulfate glycosaminoglycans

“…CS consists of a repeating disaccharide unit (‐β‐1, 4‐GlcA‐β‐1, 3‐GalNAc‐, GlcA = glucuronic acid, GalNAc = N‐acetylgalactosamine), where the positions O‐4 and/or O‐6 of the GalNAc units are commonly sulfated. According to the different sulfation patterns, the structurally‐heterogeneous CS has been mainly divided into four types: chondroitin sulfate A (CSA) = GlcA‐GalNAc (4S), chondroitin sulfate C (CSC) = GlcA‐GalNAc (6S), chondroitin sulfate D (CSD) = GlcA (2S)‐GalNAc (6S), and chondroitin sulfate E (CSE) = GlcA‐GalNAc (4S, 6S) (Mende et al, ). Sulfation pattern impacts the CS bioactivities and application areas.…”

Chemical Synthesis of Modified Hyaluronic Acid Disaccharides

“…The polysaccharide itself consists of ad isaccharide repeating unit composed of b-d-glucuronic acid (GlcA) and N-acetyl-b-d-glucosamine (GlcNAc) with the following structure motif:[ ( b1!4)-GlcA-(b1!3)-GlcNAc-] n (Figure 1). [2] As ar esult of different types of hydrogen bonds, the polysaccharide is able to form very complex secondary and tertiary structures in solution. [4] This structural order in combination with the polyelectrolyte nature of hyaluronic acid polymers induce its unique viscoelastic properties [5] as well as its ability to absorb huge amounts of water.…”

Heparin-Based Nanoparticles: An Overview of Their Applications

“…These nanoparticles were conjugated to a collagen matrix of cell surface using a polymer linker which remained stable in in vivo conditions and used as a Magnetic Resonance Imaging (MRI) agent, offering an alternative to endocytosis [94]. As for targeting, GonÇ alves et al developed heparin-chitosan nanoparticles labeled with rhodamine activated derivative (5 [6]-carboxy-X-rhodamine N-succinimidyl ester (ROX)). The entire system was named CHROX.…”