Iodoacetate
Encyclopedia
Iodoacetic acid is a derivative of acetic acid
. It is a toxic compound, because, like many alkyl halides, it is an alkylating agent. It reacts with cysteine
residues in proteins. It is often used to modify SH-groups to prevent the re-formation of disulfide bond
s after the reduction of cystine
residues to cysteine during protein
sequencing.
, with the mechanism of inhibition occurring from alkylation of the catalytic cysteine residue (see schematic). In comparison with its amide derivative, iodoacetamide
, iodoacetate reacts substantially faster. This observation appears contradictory to standard chemical reactivity, however the presence of a favourable interaction between the positive imidazolium ion of the catalytic histidine and the negatively charged carboxyl-group of the iodoacetate is the reason for the increased activity of iodoacetate.
Acetic acid
Acetic acid is an organic compound with the chemical formula CH3CO2H . It is a colourless liquid that when undiluted is also called glacial acetic acid. Acetic acid is the main component of vinegar , and has a distinctive sour taste and pungent smell...
. It is a toxic compound, because, like many alkyl halides, it is an alkylating agent. It reacts with cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
residues in proteins. It is often used to modify SH-groups to prevent the re-formation of disulfide bond
Disulfide bond
In chemistry, a disulfide bond is a covalent bond, usually derived by the coupling of two thiol groups. The linkage is also called an SS-bond or disulfide bridge. The overall connectivity is therefore R-S-S-R. The terminology is widely used in biochemistry...
s after the reduction of cystine
Cystine
Cystine is a dimeric amino acid formed by the oxidation of two cysteine residues that covalently link to make a disulfide bond. This organosulfur compound has the formula 2. It is a white solid, and melts at 247-249 °C...
residues to cysteine during protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
sequencing.
Peptidase inhibitor
Iodoacetate is an irreversible inhibitor of all cysteine peptidasesCysteine protease
Proteases are enzymes that degrade polypeptides. Cysteine proteases have a common catalytic mechanism that involves a nucleophilic cysteine thiol in a catalytic dyad. The first step is deprotonation of a thiol in the enzyme's active site by an adjacent amino acid with a basic side chain, usually a...
, with the mechanism of inhibition occurring from alkylation of the catalytic cysteine residue (see schematic). In comparison with its amide derivative, iodoacetamide
Iodoacetamide
2-Iodoacetamide is an alkylating agent used for peptide mapping purposes. Its actions are similar to those of iodoacetate. It is commonly used to bind covalently with the thiol group of cysteine so the protein cannot form disulfide bonds. Also used in ubiquitin studies as an inhibitor of...
, iodoacetate reacts substantially faster. This observation appears contradictory to standard chemical reactivity, however the presence of a favourable interaction between the positive imidazolium ion of the catalytic histidine and the negatively charged carboxyl-group of the iodoacetate is the reason for the increased activity of iodoacetate.
Possible cancer therapy
Several studies have shown iodoacetate has anti-tumor effects. In 2002 Dr. Fawzia Fahim showed that "a single IAA treatment of tumor-bearing mice significantly increased the levels of plasma lactate dehydrogenase (LDH) activity, while it also significantly decreased the levels of plasma glucose and liver total protein, RNA and DNA, compared to normal controls." In 1975 Melvin S. Rhein, Joyce A. Filppi and Victor S. Moore showed that iodoacetate improved the immune response of bone marrow. In 1966 Charles A. Apffel, Barry G. Arnason & John H. Peters showed anti-tumor activity for iodoacetate.External links
- The MEROPSMeropsMerops may refer to:* Merops , a genus of bee-eaters.* MEROPS, an on-line database for peptidases.It may also refer to several figures from Greek mythology:* King of Ethiopia, husband of Clymene, who lay with Helios and bore Phaethon...
online database for peptidases and their inhibitors: Iodoacetate