Bioengineered heparins and heparan sulfates

Abstract

Heparin and heparan sulfates are closely related linear anionic polysaccharides, called glycosaminoglycans, which exhibit a number of important biological and pharmacological activities. These polysaccharides, having complex structures and polydispersity, are biosynthesized in the Golgi of animal cells. While heparan sulfate is a widely distributed membrane and extracellular glycosaminoglycan, heparin is found primarily intracellularly in the granules of mast cells. While heparin has historically received most of the scientific attention for its anticoagulant activity, interest has steadily grown in the multi-faceted role heparan sulfate plays in normal and pathophysiology. The chemical synthesis of these glycosaminoglycans is largely precluded by their structural complexity. Today, we depend on livestock animal tissues for the isolation and the annual commercial production of hundred ton quantities of heparin used in the manufacture of anticoagulant drugs and medical device coatings. The variability of animal-sourced heparin and heparan sulfates, their inherent impurities, the limited availability of source tissues, the poor control of these source materials and their manufacturing processes, suggest a need for new approaches for their production. Over the past decade there have been major efforts in the biotechnological production of these glycosaminoglycans, driven by both therapeutic applications and as probes to study their natural functions. This review focuses on the complex biology of these glycosaminoglycans in human health and disease, and the use of recombinant technology in the chemoenzymatic synthesis and metabolic engineering of heparin and heparan sulfates.

Carbohydrate‐based nanomaterials for biomedical applications

“…GAGs are widely present on the mammalian cell surface as well as in the extracellular matrix. For this reason, GAGs are popular materials for biomedical studies, as drugs or carriers in drug delivery systems (Fu, Suflita, & Linhardt, ; G. Huang & Huang, ; Köwitsch, Zhou, & Groth, ; Rnjak‐Kovacina, Tang, Whitelock, & Lord, ; Rodriguez‐Torres, Acosta‐Torres, & Diaz‐Torres, ).…”

Extraction, purification, characterization, anticoagulant activity, and anticoagulant mechanism of polysaccharides from the heads of Hypomesus olidus

“…Heparin, used in the treatment of cardiovascular diseases and prevention of thrombosis, is the most commonly used anticoagulant drug (Croles et al, ; Hao, Xu, Yu, & Zhang, ; Kawano et al, ). But it could produce side effects such as bleeding and thrombocytopenia (Fu, Suflita, & Linhardt, ; Risch, Fischer, Herklotz, & Huber, ; Roberts and Susan, ). Therefore, it is necessary to discover new and safe anticoagulant active ingredients without the risk of bleeding from natural products.…”

Engineered heparins as new anticoagulant drugs

“…Heparin and HS are biosynthesized in the endoplasmic reticulum (ER) and Golgi through the same pathway . The heparin core protein, serglycin, is first biosynthesized in the rough ER .…”