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• W4236098000 abstract "The idea of a drug interfering with the utilization of an essential metabolite is older than the subject of chemotherapy itself, and probably celebrated its fiftieth birthday about a month ago. In 1898 Ehrlich, in a letter to his cousin Carl Weigert, indicated clearly the conception which has attracted so much attention in recent years. In his example Ehrlich pictured, for the sake of argument, an aldehyde group protruding from a cell having the particular function of fixing a specific nutritional factor for that cell. He then pictured a harmless compound, circulating in the blood, having the property of combining with this aldehyde group and so rendering the latter unavailable for its normal role. He goes on to say that the cell in this specific way must go hungry and can only survive if it can throw out another side-chain carrying an aldehyde group (Heymann 1928). In modern nomenclature, a drug may occupy the site on an enzyme normally utilized by an essential metabolite and, as Fildes pointed out in 1940, if the drug is similar to the metabolite in general structure, yet not sufficiently similar to have the same biological action, it has a good chance of interfering with that metabolite by competing with it for its enzyme. I do not know if any writers on this subject go beyond this and enquire what happens to the drug, but it was suggested by Andrewes, King & Walker (1946) in discussing the action of p -sulphonamidobenzamidine and related compounds in experimental typhus that these drugs were incorporated into functionally useless structures by the organism with consequent squandering of its synthetic resources. Such a view may sound heretical to many enzymologists but we have a good analogy in the work described from the Lilly Research Laboratories (1945), where unnatural phenylacetic acids were presented to Penicillium notatum , either as ethanolamides or as amides with DL-valine, with consequent production of analogues of penicillin G in which the phenylacetyl group of the latter has been replaced by the corresponding acyl radicals from the unnatural phenylacetic acids; incidentally, it would be a great convenience in the nomenclature of the penicillins if a trivial name could be adopted for the amine of which penicillin G is the phenylacetyl derivative. Similarly, with the knowledge that p -aminobenzoic acid turns up in the folic acid molecule, it seems likely that sulphonamides may be built up into functionally useless structures and that they do not merely compete with p -aminobenzoic acid for a site on the enzyme utilizing p-aminobenzoic acid in the fashion of a game of musical chairs. Forrest & Walker (1948) have suggested that the three carbon atoms of pteroic acid indicated in heavy type may be derived from a triose, and the suggestion by O’Meara, McNally & Nelson (1947) that the strongly-reducing non-sulphydryl substance found in bacterial cultures during the logarithmic phase of growth might be reductone, CHO. C(OH):CH(OH), seemed to us to be significant in that connexion." @default.
• W4236098000 created "2022-05-12" @default.
• W4236098000 date "1949-06-23" @default.
• W4236098000 modified "2023-10-18" @default.
• W4236098000 title "General Discussion" @default.
• W4236098000 cites W136526989 @default.
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• W4236098000 doi "https://doi.org/10.1098/rspb.1949.0017" @default.
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