Bolton-Hunter reagent structure

Figure 12.7 The Bolton-Hunter reagent may be radioiodinated at its phenolic ring structure prior to reaction with an amine-containing molecule to form an amide bond modification.

A water-soluble version of the original Bolton-Hunter reagent also is available, called sulfo-SHPP (Thermo Fisher). This compound contains a negatively charged sulfonate group on the NHS ring structure, which provides enough hydrophilicity to allow direct addition to aqueous reaction mediums. 

N-succinimydyl propionate reacts in an analogous manner to the Bolton-Hunter reagent. It has the advantage of being a smaller molecule than the Bolton-Hunter reagent and hence causes less alterations to the protein structure... 

Fig. 1. Chemical structures (I), I-labeled iV-succinimidyl 3-(4-hydroxyphenyl)pro-pionate (Bolton-Hunter reagent) (II), di- I-labeled methyl p-hydroxybenzimidate (III), I-labeled diazotized aniline.

In vivo, deiodination is thought to be due to enzymes, deiodases. Indeed, due to a structural analogy with thyroid hormones, molecules labeled with Bolton-Hunter reagent or iodinated on a tyrosine moiety are recognized and quickly metabolized. Three classes of deiodases are known. Type I enzymes are mainly located in the liver, kidneys, and skeletal muscle, and deiodinate in the 5 and 5 positions of the tyrosine ring. Type II enzymes, in the brain, pituitary tissue and brown fat, and type III, localized in the central nervous system, both catalyze deiodination on the tyrosine 5 position. 

Chemical structures of representative heterobifunctional reagents for the radioiodination of proteins, (a) Bolton and Hunter reagent, (b) water-soluble Bolton and Hunter reagent,... 

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