Iodoacetic anhydride

For coupling with cysteine residue, the glycosylamine could be trapped by iodoacetic anhydride. Such method was applied with glucose, maltose and maltotriose after their transformation in the corresponding glycosylamines. The study is part of a work devoted to the S3mthesis of... 

The PEGylation reactions with 38 are usually performed using an excess of the reagent in a darkened flask, in order to Emit the formation of iodine, which can react with other amino acids. mPEG-iodoacetamide is a commercially available reagent that can be prepared by the reaction of mPEG-amine 42 with iodoacetic anhydride in diox-ane [178]. Examples of the use of 38 include the PEGylation of acyl-coenzyme A and cholesterol acyltransferase [198]. 

Figure 6. Modifications of imidazole groups (a) ethoxyformic anhydride (diethylpyrocarbonate) (b) iodoacetic acid (c) iodination.

Iodoacetic acid [64-69-7] (ICH2COOH), mol wt 185.95, C2H3I02, is commercially available. The colorless, white crystals (mp 83 °C) are unstable upon heating. It has a K of 7,1 x 10-4. Iodoacetic acid is soluble in hot water and alcohol, and slightly soluble in ethyl ether. Iodoacetic acid can be reduced with kydroiodic acid at 85°C to give acetic acid and iodine (57). Iodoacetic acid cannot be prepared by the direct iodination of acetic acid (58), but has been prepared by iodination of acetic anhydride in the presence of sulfuric or nitric acid (59). Iodoacetic acid can also be prepared by reaction of chloroacetic or bromoacetic acid with sodium or potassium iodide (60). 

A carboxyl group can be introduced in almost any compound by various methods. In cases where a free thiol is present, the carboxyl group can be introduced easily by reaction with bromo- or iodoacetic acid. This reaction is very mild and is usually performed at pH around 8-9. When the hapten contains a hydroxyl group, carboxylic acid may be introduced by one of the following methods (a) carboxymethylation of the hydroxyl group with bromo- or iodoacetic acid (b) esterification with dicarboxylic acid anhydrides, such as succinic anhydride, to yield hemi-succinates, which are unstable above pH 9 (c) reaction with phosgene, which results in the formation of chlorocarbonates. ... 

The following polypeptide was treated with 2-mercaptoethanol and then with iodoacetic acid. After reacting with maleic anhydride, the peptide was hydrolyzed by trypsin. (Treatment with maleic anhydride causes trypsin to cleave a peptide only at arginine residues.)... 

Poly-L-cysteine (XXXIV) was prepared by polymerization of S-carbobenzoxy-N-carboxy-L-cysteine anhydride (XXXIII), followed by reduction with sodium in liquid ammonia 47). The reactivity of the thiol groups in this polymer toward iodoacetic add indicated that quantitative liberation of mercapto groups had beat effected but selective reactivity was observed with methyl mercuric nitrate in the presence of sodium nitroprusside, an internal indicator. These reactivity differences result from sterk exclusion of the nitroprusside dye from about one third of the available mercaptan moities. Thus the concept of sluggish-SH groups in a protein has been demonstrated with a synthetic homopolymer. 

Fig. 8.9. Chemical reactivity of individual amino acid side chains in native elastase. The reagents used were [ C]acetic anhydride (A) [ " C]dimethyl sulfate ( ) and [ " C]iodoacetate ( ). The reference value for a totally accessible group was the chemical reactivity determined in the denatured and reduced form of the protein. The lower part of the figure indicates all the modified side chains along the sequence (from Ghelis, 1980).

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