Iodoacetamide

Iodoacetamide
Names
	Preferred IUPAC name 2-Iodoacetamide
	Other names IAA
Identifiers
CAS Number	144-48-9 ;
3D model (JSmol)	Interactive image;
ChEMBL	ChEMBL276727 ;
ChemSpider	3596 ;
ECHA InfoCard	100.005.119
EC Number	205-630-1;
IUPHAR/BPS	6271;
PubChem CID	3727;
RTECS number	AC4200000;
UNII	ZRH8M27S79 ;
CompTox Dashboard (EPA)	DTXSID9020742 ;
	InChI InChI=1S/C2H4INO/c3-1-2(4)5/h1H2,(H2,4,5) Key: PGLTVOMIXTUURA-UHFFFAOYSA-N ; 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). verify (what is ?) Infobox references

Iodoacetamide (IAA) is an organic compound with the chemical formula I C H₂CO 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]

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

^ 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.
^ 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.
^ 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.
^ 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.
^ 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: [1]

[Krüger_Hung_Edelson-Averbukh_Lehmann_2005_pp._1709–1716-1] 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.

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