PEGylation at Arginine

A more convenient method for the site-selective PEGylation of arginine has only recently been disclosed [255,256]. The process relies on the thermodynamic selectivity obtained upon reaction of the protein with methyl glyoxal analog 72. In aqueous solution, dimethyl acetal derivative 72 is in equilibrium with the unprotected forms, which are the actual PEGylating reagents (Equation 3.41). 

A detailed study of the reaction of methyl glyoxal 72 with iV-acetyl arginine and iV-acetyl cysteine has been performed and, importantly, it has been demonstrated that with reagent 72, PEGylation at lysine residues does not occur [256]. 

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