Robert H. Abeles, Ph.D.


Robert Heinz Abeles was born in Vienna, Austria on January 14, 1926. As a boy, he emigrated to the United States and settled in Chicago, Illinois. He was educated at the University of Chicago, where he received the M.S. degree in 1950. He went on to earn a Ph.D. degree in Biochemistry at the University of Colorado in 1955, and he did postdoctoral work in Chemistry with F.H. Westheimer at Harvard University. He was an Assistant Professor of Chemistry at The Ohio State University from1957 to 1960, Assistant and Associate Professor of Biological Chemistry at the University of Michigan from 1960 to 1964, and Associate Professor and Professor of Biochemistry at Brandeis University from 1964 to his death on June 18, 2000. Abeles received many honors during his career, including the Edward E. Swissman-Bristol Myers Award in Medicinal Chemistry in 1987, the Repligen Award in the Chemistry of Biological Processes in 1988, the Alfred E. Bader Award of the ACS in 1990, the William Rose Award of the ASBMB in 1994, an Alexander von Humboldt Senior Scientist Award from the German government, and an Honorary Doctor of Science degree from the University of Chicago, as well as election to the National Academy of Sciences and the American Academy of Arts and Sciences.

Professor Abeles was an imaginative and creative force in the field of mechanistic enzymology. Abeles' work relied on the confluence of chemistry and biology long before the interface of these two disciplines came into vogue. He investigated enzymatic reactions that posed mechanistic puzzles to organic chemists, and his contributions include many 'firsts'. He first discovered the mechanism of action of the vitamin B12 coenzyme adenosylcobalamin, the development of suicide inactivators for enzymes as pharmaceutical targets, the first discovery of a transition state analog inhibitor, the first discovery of the retaining double displacement mechanism in glycosyltransferases, and the first elucidation of the mechanisms of action of many enzymes that catalyze chemically novel reactions. Abeles discovered the pathway from methylthioadenosine to methionine, and he then discovered the enzymatic production of carbon monoxide, a regulator of blood-vessel relaxation.

Abeles began his career by investigating the enzymatic dehydration of 1,2-propanediol to propionaldehyde in bacteria, as a possible example of an intramolecular hydride shift. In this research he discovered and characterized dioldehydrase, which he showed to be one of the first enzymes to require a vitamin B12 coenzyme, adenosylcobalamin. The molecular basis for the action of this coenzyme was unknown. Abeles soon disproved the hypothesis of the 1,2-hydride shift and proceeded to elucidate the mechanistic role of adenosylcobalamin in hydrogen transfer. Between 1964 and 1971 every significant new finding regarding the mechanism of action of adenosylcobalamin was first discovered in Abeles' laboratory. All findings were quickly generalized in other laboratories for other adenosylcobalamin-dependent reactions. As one step in his research on dioldehydrase in the mid-1960s, Abeles discovered his first suicide inactivator, glycolaldehyde, which inactivated dioldehydrase. Abeles' work on dioldehydrase not only influenced research in biochemistry, it also introduced new chemistry, unlike any that had been described in the classical literature.

In the 1970s, Abeles turned his skills and intellect to the problem of designing and investigating specific inhibitors of enzymes. Such inhibitors are fundamental starting points in drug discovery. This work was directed toward the long-term goal of finding ways to proceed rationally to the design of pharmacological agents that might find use in the treatment of disease. Dr. Abeles was an innovative and imaginative force in this field, and his work stimulated research in the pharmaceutical industry and academia. Abeles designed potent inhibitors of proteases, carboxylases, oxidases, isomerases, and dehydrogenases. Many of these inhibitors were suicide inactivators. These compounds underwent initial steps of the normal catalytic mechanisms, leading to species that deviated from the natural course of events and led to destruction of enzymatic activity; thus, the enzyme catalysed its own death. Suicide inactivators revealed information about enzymatic mechanisms, and provided the specificity necessary for drug development.

Abeles' magnetic speaking style, originality, and creativity drew students into his orbit. He had the ability to define the essence of a research problem and then to solve it. He trained three generations of graduate and postdoctoral students to be leaders in the science of mechanistic enzymology.