ABSTRACT
Although the selective modification of carboxyl groups was the subject of one of the early attempts to adapt organic chemistry to the systematic study of the relationship between structure and function in proteins, serious study in the area did not develop at a significant rate until the application of water soluble carbodiimide-mediated attack by a protein-bound carboxyl group on a suitable nucleophile by Koshland and Hoare. Indeed, there are examples of carboxyl group modification with reagents expected to react far more effectively with the other nucleophiles. An example of this is the reaction of iodoacetamide with ribonuclease T1 to form the glycolic acid derivative of the glutamic acid residue as elegantly shown by Takahashi and co-workers. Active-site directed reactions with reactive epoxy functional groups have proved useful in several studies of the role of the carboxyl groups in the proteins.
