2-Iodoacetamide is an
alkylating agent
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting al ...
used for
peptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A ...
mapping purposes. Its actions are similar to those of
iodoacetate
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 ...
. It is commonly used to bind covalently with the
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 ...
group of
cysteine
Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile.
When present as a deprotonated catalytic residue, sometime ...
so the protein cannot form
disulfide bond
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 ...
s. Also used in
ubiquitin
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fo ...
studies as an inhibitor of
deubiquitinase enzymes (DUBs) because it alkylates the cysteine residues at the DUB active site.
Peptidase inhibitor
Iodoacetamide is an irreversible inhibitor of all cysteine peptidases, with the mechanism of inhibition occurring from alkylation of the catalytic cysteine residue (see schematic). In comparison with its acid derivative, iodoacetate, iodoacetamide 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 relative activity of iodoacetamide.
Protein mass spectrometry
It is commonly used during the sample preparation for de novo (peptide) sequencing with
protein mass spectrometry
Protein mass spectrometry refers to the application of mass spectrometry to the study of proteins. Mass spectrometry is an important method for the accurate mass determination and characterization of proteins, and a variety of methods and instru ...
, but recent critics suggest to avoid the use of it
References
{{Reflist
External links
*The
MEROPS
MEROPS is an online database for peptidases (also known as proteases, proteinases and proteolytic enzymes) and their inhibitors. The classification scheme for peptidases was published by Rawlings & Barrett in 1993, and that for protein inhibitor ...
online database for peptidases and their inhibitors
Alkylating agents
Organoiodides
Acetamides