ABSTRACT
The specific chemical modification of proteins was useful in early studies on the relationship between the structure and function of proteins. However, specific chemical modification has been largely supplanted by the site-specific modification of proteins using recombinant DNA technology. Shaw and coworkers continued their work on the reaction of sulfonyl esters with thrombin and other tryptic-like serine proteases with derivatives of benzene sulfonic acid and phenylmethylsulfonic acid, which were intended to evaluate reagent length and position of the basic substituent on the aromatic ring. Histidine is found at the active of site of more than 50% of characterized enzymes. Acylation of a nitrogen on the imidazole ring is another approach to the chemical modification of histidine. Lundblad and observed that N-acetylation inhibited the clotting activity of thrombin with a minimal effect on esterase activity. The amino terminal of the B-chain of thrombin, as with serine proteases, is bound up in an internal salt bridge and is unavailable for chemical modification.
