Iodoacetamide

Iodoacetamide

Skeletal formula
Space-filling model
Names
Preferred IUPAC name 2-Iodoacetamide
Other names IAA [1]
Identifiers
CAS Number	144-48-9  Y
3D model (JSmol)	Interactive image
ChEMBL	ChEMBL276727  Y
ChemSpider	3596  Y
ECHA InfoCard	100.005.119
EC Number	205-630-1
IUPHAR/BPS	6271
PubChem CID	3727
RTECS number	AC4200000
UNII	ZRH8M27S79  Y
CompTox Dashboard (EPA)	DTXSID9020742
InChI InChI=1S/C2H4INO/c3-1-2(4)5/h1H2,(H2,4,5) Y Key: PGLTVOMIXTUURA-UHFFFAOYSA-N Y InChI=1/C2H4INO/c3-1-2(4)5/h1H2,(H2,4,5) Key: PGLTVOMIXTUURA-UHFFFAOYAE
SMILES C(C(=O)N)I
Properties
Chemical formula	ICH2CONH2
Molar mass	184.964 g·mol−1
Appearance	white crystals (yellow colouration indicates the presence of iodine)
Melting point	94 °C (201 °F; 367 K)
Hazards
NFPA 704 (fire diamond)	3 0 1
Safety data sheet (SDS)	MSDS 1, MSDS 2
Related compounds
Related compounds	Acetamide Fluoroacetamide Chloroacetamide Bromoacetamide Iodoacetic acid
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y  verify  (what is  YN ?) Infobox references

Iodoacetamide (IAA) is an organic compound with the chemical formula I C H ₂CO NH₂. It 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. ^{[2] [3]} It is also used in ubiquitin 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. ^[4]

Mechanism of irreversible inhibition of cysteine peptidases with iodoacetamide.

Protein mass spectrometry

It is commonly used during the sample preparation for de novo (peptide) sequencing with protein mass spectrometry, but recent critics suggest to avoid the use of it. ^[5]

References

1. Krüger, Ralf; Hung, Chien-Wen; Edelson-Averbukh, Marina; Lehmann, Wolf D. (2005). "Iodoacetamide-alkylated methionine can mimic neutral loss of phosphoric acid from phosphopeptides as exemplified by nano-electrospray ionization quadrupole time-of-flight parent ion scanning". Rapid Communications in Mass Spectrometry. 19 (12). Wiley: 1709–1716. Bibcode:2005RCMS...19.1709K. doi:10.1002/rcm.1976. ISSN   0951-4198. PMID   15912474.
2. Smythe CV (1936). "The reactions of Iodoacetate and of Iodoacetamide with various Sulfhydryl groups, with Urease, and with Yeast preparations". J. Biol. Chem. 114 (3): 601–12. doi: 10.1016/S0021-9258(18)74789-3 .
3. Anson ML (1940). "The reactions of Iodine and Iodoacetamide with native Egg Albumin". J. Gen. Physiol. 23 (3): 321–31. doi:10.1085/jgp.23.3.321. PMC   2237930 . PMID   19873158.
4. Polgar, L (1979). "Deuterium isotope effects on papain acylation. Evidence for lack of general base catalysis and for enzyme-leaving group. interaction". Eur. J. Biochem. 98 (2): 369–374. doi: 10.1111/j.1432-1033.1979.tb13196.x . PMID   488108.
5. Müller (2017). "Systematic Evaluation of Protein Reduction and Alkylation Reveals Massive Unspecific Side Effects by Iodine-containing Reagents". Molecular & Cellular Proteomics. 16 (7): 1173–1187. doi: 10.1074/mcp.M116.064048 . PMC   5500753 . PMID   28539326.

External links

• The MEROPS online database for peptidases and their inhibitors: