Abzymes, derived from antibody enzyme, were first obtained in 1986 against transition state analogs. The research groups of Schultz (1) and Lerner (2) showed that antibodies raised to tetrahedral, negatively charged phosphate and phosphonate transition state analogs could selectively catalyze the hydrolysis of carbonates and esters, respectively (1, 2). Since 1986, abzymes have been discovered and generated that catalyze a wide array of chemical reactions ranging from transesterification to b-elimination. The specificity of these antibody-catalyzed reactions rivals or exceeds those of enzymatic reactions (3).
The stabilization of a transition state by an antibody creates an enzyme, known as the abzyme. In the example below, the analog shown on the left was covalently linked to a protein and used as an antigen to generate an antibody that binds tightly to the region of the analog shown in yellow. Because this antibody also bound tightly to the transition state in the hydrolysis of an amide bond reaction, it was found to function as an enzyme that efficiently catalyzed the hydrolysis of the amine bond in the molecule shown on the right.(4)
In 1989, Paul et al. discovered the first natural abzyme, a catalytic IgG specifically hydrolyzing intestinal vasoactive peptide (5). Numerous natural catalytic antibodies were detected afterwards in serum of patients with several autoimmune and viral disorders, as well as in the milk of healthy women. Abzymes that occur in the milk of healthy human mothers include IgA and/or IgG possessing DNase and RNase, amylolitic or ATPase activities, and protein and lipid kinase activities. Human milk abzymes show specific activities significantly higher than those found in most autoimmune diseases or viral disorders. (6) There are many possible biotechnological and medical applications utilizing natural abzymes left unexplored, as well as unanswered questions about their role in the pregnant mother and in autoimmune and viral disorders. Questions about Abzymes
References:
1. Pollack SJ, Jacobs JW, Schultz PG. 1986. Selective chemical catalysis by an antibody. Science 234:1570- 3.
2. Tramontano A, Janda KD, Lerner RA. 1986. Catalytic antibodies. Science 234:1566-70.
3. Lerner RA, Benkovic SJ, Schultz PG. 1991. At the crossroads of chemistry and immunology: catalytic antibodies. Science 252:659-67.
4. Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD. 1994. Molecular biology of the cell, 3rd ed. New York: Garland Publishing.
5. Paul S, Volle DJ, Beach CM, Johnson DR, Powell MJ, Massey RJ. 1989. Catalytic hydrolysis of vasoactive intestinal peptide by human autoantibody. Science 244:1158-62.
6. Nevinsky GA, Buneva VN. 2003. Catalytic antibodies in healthy humans and patients with autoimmune and viral diseases. J Cell Mol Med 7(3):265-76.
