Heparinoids are

glycosaminoglycan Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case o ...

s which are chemically and pharmacologically related to

heparin Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Heparin is a blood anticoagulant that increases the activity of antithrombin. It is used in the treatment of myocardial infarction, ...

. 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 464-amino-acid protein produced by the liver. It contains three disulfide bonds and a total of four possible glycosylation sites. α-An ...

. 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 Chymases (, mast cell protease 1, skeletal muscle protease, skin chymotryptic proteinase, mast cell serine proteinase, skeletal muscle protease) are a family of serine proteases found primarily in mast cells, though also present in basophil granul ...

, which directly binds to heparin.

Sulfated polysaccharides

From animal tissues

Dermatan sulfate Dermatan sulfate is a glycosaminoglycan (formerly called a mucopolysaccharide) found mostly in skin, but also in blood vessels, heart valves, tendons, and lungs. It is also referred to as chondroitin sulfate B, although it is no longer classifi ...

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 An antithrombotic agent is a drug that reduces the formation of blood clots ( thrombi).http://cancerweb.ncl.ac.uk/cgi-bin/omd?antithrombotic Antithrombotics can be used therapeutically for prevention ( primary prevention, secondary prevention) or ...

agent.

Chondroitin sulfate Chondroitin sulfate is a sulfated glycosaminoglycan (GAG) composed of a chain of alternating sugars (N-Acetylgalactosamine, N-acetylgalactosamine and glucuronic acid). It is usually found attached to proteins as part of a proteoglycan. A chondroit ...

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. It shares the common name " giant African snail" with other species o ...

''.

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 whe ...

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

Chitin Chitin (carbon, C8hydrogen, H13oxygen, O5nitrogen, N)n ( ) is a long-chain polymer of N-Acetylglucosamine, ''N''-acetylglucosamine, an amide derivative of glucose. Chitin is the second most abundant polysaccharide in nature (behind only cell ...

, a component of insect shells and fungal structures, can be de-''N''-acetylated to form

chitosan Chitosan is a linear polysaccharide composed of randomly distributed β-(1→4)-linked D-glucosamine (deacetylated unit) and ''N''-acetyl-D-glucosamine (acetylated unit). It is made by treating the chitin shells of shrimp and other crusta ...

, which when sulfated has a significant chemical similarity to heparin. In fact, it inhibits thrombin by affecting ATIII.

Lepirudin Lepirudin is an anticoagulant that functions as a direct thrombin inhibitor. Brand name: Refludan, Generic: Lepirudin rDNA for injection. Lepirudin is a recombinant hirudin derived from yeast cells. Lepirudin is almost identical to hirudin ext ...

is a recombinant preparation of the polypeptide anticoagulant secreted by leeches and is used in patients with heparin induced thrombocytopenia.

From plant sources

Fucoidan Fucoidan is a long chain sulfated polysaccharide found in various species of brown algae. Commercially available fucoidan is commonly extracted from the seaweed species ''Fucus vesiculosus'' (Wrack (seaweed), wracks), ''Cladosiphon okamuranus'', '' ...

is a polymer composed of sulfated L-fucose.

Carrageenan Carrageenans or carrageenins ( ; ) are a family of natural linear sulfation, sulfated polysaccharides. They are extracted from red algae, red edible seaweeds. Carrageenans are widely used in the food industry, for their gelling, thickening, an ...

s are isolated from algae.

Hyaluronan Hyaluronic acid (; abbreviated HA; conjugate acid, conjugate base hyaluronate), also called hyaluronan, is an anion#Anions and cations, anionic, Sulfation, nonsulfated glycosaminoglycan distributed widely throughout connective tissue, connective ...

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 Alginic acid, also called algin, is a naturally occurring, edible polysaccharide found in brown algae. It is hydrophilic and forms a viscous gum when hydrated. When the alginic acid binds with sodium and calcium ions, the resulting salts are kn ...

functions as a heparinoid when it is sulfated. Pentosan from the bark of ''

Fagus sylvatica ''Fagus sylvatica'', the European beech or common beech, is a large, graceful deciduous tree in the Fagaceae, beech family with smooth silvery-gray bark, large leaf area, and a short trunk with low branches. Description ''Fagus sylvatica'' i ...

'', when sulfated, acts with one-tenth 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

* {{Authority control Glycosaminoglycans