Cystamine (2,2'-dithiobisethanamine) is an organic

disulfide In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...

. It is formed when

cystine Cystine is the oxidized derivative of the amino acid cysteine and has the formula (SCH2CH(NH2)CO2H)2. It is a white solid that is poorly soluble in water. As a residue in proteins, cystine serves two functions: a site of redox reactions and a mec ...

is heated, the result of decarboxylation. Cystamine is an unstable liquid and is generally handled as the dihydrochloride salt, C₄H₁₂N₂S₂·2HCl, which is stable to 203-214 °C at which point it decomposes. Cystamine is toxic if swallowed or inhaled and potentially harmful by contact.

Structure and synthesis

Cystamine is an organic disulfide which is formed when Cystine is heated as a result of decarboxylation. It is often used as sulfhydryl reagent, enzyme inhibitor and radiation-protective agent.

Thiol In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl gro ...

s can be synthesized to disulfides like cystamine through chemical oxidation with various oxidizing agents (molecular oxygen, metal ion, metal oxide, DMSO, nitric oxide, halogen and sodium perborate), through electrochemical oxidation and through borohydride exchange resin (BER)-transition metal salts systems (like BER-CuSo4).

Uses

Cystamine dihydrochloride is a useful reagent to derivatize various polymer monoliths for hydrophilic interaction liquid chromatography, as a crosslinking agent in the development of polymer hydrogels, and as a functional group in nanoparticles developed for siRNA and DNA delivery. It has also been studied as a potential

radioprotective Nuclear safety is defined by the International Atomic Energy Agency (IAEA) as "The achievement of proper operating conditions, prevention of accidents or mitigation of accident consequences, resulting in protection of workers, the public and the ...

agent. Cystamine has also been studied as a potential medicinal compound in the case of

Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an uns ...

, Alzheimer's disease, carbon tetrachloride liver damage, and inhibition of erythrocyte sickling

Interactions

Cystamine has been shown to bind reversibly with purified DNA ''in vitro'', and imparts a radiation-protective effect to treated DNA. However, ''in vitro'' cell culture experiments on mammalian cells treated with cystamine failed to show a radiation-protective effect, whereas treatment with cysteamine did. Furthermore, cystamine is also able to bind to

nucleoprotein Nucleoproteins are proteins conjugated with nucleic acids (either DNA or RNA). Typical nucleoproteins include ribosomes, nucleosomes and viral nucleocapsid proteins. Structures Nucleoproteins tend to be positively charged, facilitating int ...

s. The nucleic acids that form from binding to DNA are more stable then unbound nucleic acids. Binding of cystamine to nucleoproteins makes them precipitate. The disulfides than binds to DNA and precipitate nucleoproteins have an analogous interaction like

cadaverine Cadaverine is an organic compound with the formula (CH2)5(NH2)2. Classified as diamine, it is a colorless liquid with an unpleasant odor. It is present in small quantities in living organisms but is often associated with the putrefaction of an ...

and

spermidine Spermidine is a polyamine compound () found in ribosomes and living tissues and having various metabolic functions within organisms. It was originally isolated from semen. Function Spermidine is an aliphatic polyamine. Spermidine synthase (SP ...

with DNA. The affinity of cystamine to DNA plays a role in the toxicity and radioprotecting properties of cystamine. Cystamine has also been shown to interact with the production of microtubule assemblies in bovine brain tissue. The interaction of cystamine interferes with the formation of microtubules, thus acting as an anti-microtubule at low concentrations. At high concentrations cystamine induces an abnormal

tubulin Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytoske ...

polymerization. Five cystamine molecules can bind covalently to tubulin, this will cause mediated aggregation of tubulins.

Toxicity

Multiple factors of potential cystamine toxicity have been described relating to hepatoxicity, anti-coagulant activity and skin sensitisation. LD50/48H values after intravenous administration have been described for rats (97 mg/kg of body weight) and mice (155.93 mg/kg of body weight). Cystamine inhibits coagulation factor XIa and thrombin, Therefore, exhibiting anti-coagulant behavior. Furthermore, cystamine can cause liver damage by elevating cytosolic Ca²⁺ levels and subsequently activating a cytosolic proteolytic system. Skin sensitisation is a predicted effect of cystamine being a thiol.

Metabolism

Cystamine in the body is reduced into cysteamine and RS-cysteamine mixed disulfide by thiol-disulfide exchange. This is done by consumption of intracellular glutathione. Cysteamine is then oxidized to hypotaurine, this is done by the enzyme dioxygenase. The now formed hypotaurine is finally oxidized to taurine by hypotaurine dehydrogenase and the reduction of NAD+. Taurine is excreted out of the body or used in the body.

References

{{Reflist Amines Organic disulfides