Back to The Future or Play It Again Sam (with apologies to Casablanca)

As some of you may know, having finished a book on Biomarkers (due in October from CRC/Taylor and Francis) and having completed editing (with Fiona MacDonald) the 4th edition of the Handbook of Biochemistry and Molecular Biology (CRC/Taylor and Francis), I have embarked on another book on the chemical modification of biological polymers. I was acquainting myself once again with J.L Webb's treatise entitled "Enzyme and Metabolic Inhibitors" (Academic Press, 1963-1966). There is an extensive discussion of various reagents used for the modification of sulfhydryl groups including a long chapter on iodoacetate/iodoacetimide. One table showed the chronological use of iodoacetate up to 1960; I extended the information to present time. For comparison, Chemical Abstract Services (CAS, SciFinder), obtained 6039 citations for N-ethylmaleimide for 1990-2000. The 2010 citations are through August 6, 2010. There are reasons for the greater use of N-ethylmaleimide which are discussed elsewhere.

The use of iodoacetate peaked in the 1970's. Webb's work is quite useful as he covers the history of the various inhibitors. Bromoacetate, not iodoacetate, was the first haloacid used and it was in an intact animal. The use of iodoacetate (and related compounds such as bromoacetate and chloroacetate) moved from intact animals and cell homogenates to purified enzymes in the 1960's and 1970's. It was during this period of time that much of the basic work on functional group participation in enzymology was done by an outstanding group of inividuals such as Jencks, Smith, Bernard, Koshland, Fruton, Bender, and many others. The following rapid developments in crystallography provided even more insight such there was a decreasing need to study enzymes by chemical modificatin. As an exercise this afternoon while waiting for the bus, I did a quick PUBMED search on the current use of iodoacetate and found that most of the of the use is in whole cell/cell extracts. This is not intended to deprecate the current work but rather note that the emphasis in biochemistry has moved from the molecular level back to the supramolecular/integrative biology level. The ability to use immunological techiques to evaluate chemical modifications suc as nitration or reaction with 4-hydroxynonenal increases the sophistication of the experimental process. I would suggest that current investigators consult Webb's work and Zollner's Handbook of Enzyme Inhibitors, 3rd edn, Wiley-VCH, Weinheim, Germany, 1999.