Heparinoids are glycosaminoglycans which are chemically and pharmacologically related to

heparin Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treatm ...

. They include oligosaccharides and sulfated polysaccharides of plant, animal, or synthetic origin. Multiple scientific studies have been conducted on heparinoids. Heparinoids, like heparin, act by interacting with heparin binding proteins, generally through ionic interactions or hydrogen bonding. Some examples of heparin binding proteins include

antithrombin III Antithrombin (AT) is a small glycoprotein that inactivates several enzymes of the coagulation system. It is a 432-amino-acid protein produced by the liver. It contains three disulfide bonds and a total of four possible glycosylation sites. α-Ant ...

. It is thought that much protein interaction with heparin is not direct, and instead heparin binding protein actually interact with glycosaminoglycan (GAG) side chains or mucins bound to the heparin polymer, so it is possible that heparinoids interact with these proteins in a similar way, acquiring GAG side chains in vivo. One counterexample is the protein chymase, which directly binds to heparin.

Sulfated polysaccharides

From animal tissues

Dermatan sulfate is one example of a compound that is classified as a heparinoid. It is a naturally-occurring polysaccharide of ''O''-sulfated ''N''-acetyl-D-galatosamine, L-iduronic acid, and D-glucuronic acid that has been clinically used as an antithrombotic agent. Chondroitin sulfate shows slightly less biological activity than dermatan sulfate, and is composed of O-sulfated ''N''-acetyl-D-galatosamine and D-glucuronic acid. It is theorized that this change in efficacy is related to the absence of L-induronic acid, which affects the flexibility of the polymer chain. Acharan sulfate is a heparinoid that is naturally produced by the giant African land snail, ''

Lissachatina fulica ''Lissachatina fulica'' is a species of large land snail that belongs in the subfamily Achatininae of the family Achatinidae. It is also known as the Giant African land snail.Keratan sulfate Keratan sulfate (KS), also called keratosulfate, is any of several sulfated glycosaminoglycans (structural carbohydrates) that have been found especially in the cornea, cartilage, and bone. It is also synthesized in the central nervous system w ...

is a heparinoid that is a component of cartilage. It is found in the cornea.

Chitin Chitin ( C8 H13 O5 N)n ( ) is a long-chain polymer of ''N''-acetylglucosamine, an amide derivative of glucose. Chitin is probably the second most abundant polysaccharide in nature (behind only cellulose); an estimated 1 billion tons of chit ...

, a component of insect shells and fungal structures, can be de-''N''-acetylated to form chitosan, which when sulfated has a significant chemical similarity to heparin. In fact, it inhibits thrombin by affecting ATIII. Lepirudin is a recombinant preparation of the polypeptide anticoagulant secreted by leeches and is used in patients with heparin induced thrombocytopenia.

From plant sources

Fucoidan is a polymer composed of sulfated L-fucose. Carrageenans are isolated from algae.

Hyaluronan Hyaluronic acid (; abbreviated HA; conjugate base hyaluronate), also called hyaluronan, is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is unique among glycosaminoglycans ...

functions as a heparinoid when it is sulfated. Intra-articular injections of hyaluronic acid are used to mitigate pain and treat symptoms of osteoarthritis in the knee, but such injections are correlated with increased risk of serious side effects. Alginic acid functions as a heparinoid when it is sulfated. Pentosan from the bark of '' Fagus sylvatica'', when sulfated, acts with 1/10th of the efficacy of heparin.

From microbial sources

K5 polysaccharide from E. coli acts as a heparinoid when it is sulfated.

History

Heparin was first isolated from dog liver by medical student Jay McClean in 1916. Jorpes discovered the structure of the heparin polysaccharide in 1935, identifying that it is a highly sulfated polymer of glycosaminoglycoglycan (GAG) and uronic acid. Around that time, heparin began to be used in the prophylaxis and treatment of post-operative thrombosis.

Production

There is no industrial process for the complete synthesis of heparin; heparin is isolated from animal tissue - generally bovine lung, porcine, and intestinal mucosa. Heparinoids generally are also naturally-occurring polysaccharides, and similarly need to be purified from the plant or animal tissue that produces them.

Regulation

There is no internationally accepted molecular standard for the composition of heparin, as it is a complex polymer of GAG units and uronic acids (including D-glucuronic acid, L-iduronic acid, and D-glucosamine). Position of N-acetyl, N-sulfate, and O-sulfate groups in these uronic acids can vary, as can the branching patterns of the chain. This generates an extraordinary amount of variability between molecules of heparin. Current USP standards for heparin limit levels of contamination with dermatan, chondroitin, and over-sulfated chondroitin sulfate, as well as galactosamine levels in the sample, as determined by HPLC, H-NMR, and Strong Anion Exchange Chromatography.USP Safety Data Sheet: Heparin Sodium with Oversulfated Chondroitin Sulfate. http://static.usp.org/pdf/EN/referenceStandards/msds/1304050.pdf Accessed on 11/30/2015.

References

External links

* {{Antithrombotics Glycosaminoglycans