Robert H. Abeles (1926–2000)

Abstract

approach with the inactivation of diol dehydrase by glycoladehyde in 1966. Abeles used this approach to develop inhibitors of pyridoxal phosphate containing enzymes, proteases, dehydrogenases, flavoproteins and S-adenosylhomocysteine hydrolase (again, this list is merely representative). Finally, he showed that the high affinity of the inhibitor compactin for hydroxymethylglutaryl coenzyme A reductase derives from the linkage of two separate binding sites. The clinical importance of the enzymes mentioned here should not be overlooked. Isopentenyl pyrophosphate isomerase and HMGCoA reductase catalyze reactions in cholesterol biosynthesis, pyridoxal phosphate (PLP)-dependent enzymes are found in bacterial cell-wall biosynthesis and proteases are involved in almost every physiological process. These are major targets for drug development, and Abeles' work has had an enormous impact on the pharmaceutical industry and drug design. A discussion with Abeles was always a delightful experience. He would start with the latest political joke, then go to his latest pet peeve and, finally, to science. His insights and understanding were so unique that one came always away from such a discussion having learned something new, marveling at the simplicity with which he presented the most complex problem, and knowing that a new approach had just been uncovered for that problem. His skepticism about the value of structural knowledge in enzymology was deep and critical. Nevertheless, he embraced the method in a way that has shown how the method should be used: not for the mere elucidation of three-dimensional structure but rather for the understanding of mechanistic problems and the influence of protein and the flexibility of proteins. With Abeles passing, a great intellect has been lost. His chemical intuition and his love of science influenced all who had the privilege to interact with him. He will be greatly missed.