T. S. G. Jones
Jun 1, 1949
Citations
1
Influential Citations
48
Citations
Journal
Annals of the New York Academy of Sciences
Abstract
The announcement of the discovery of “Aerosporin” by Ainsworth, Brown, and Brownlee’ and of “polymyxin” (Benedict and Langlykke? Stanley ei al.“), among the metabolic products of the organisms of the B. aerospmusB. polymyxu group, raised the inevitable question of the chemical identity of these materials. The substance polymyxin A, formerly known as “Aerosporin,” was early shown to be a basic substance forming salts with mineral acids and insoluble precipitates with acidic dyestuffs. The observation of Catch4 that the purest preparations gave the ninhydrin reaction in solution, both before and after acid hydrolysis, gave reason to suppose that part of the molecule, a t least, consisted of polypeptide. The applicatiòn of the method of partition chromatography on paper (Consden, Gordon, and Martin6) to the products of the acid hydrolysis of polymyxin A preparations by Jones6 led to the discovery of the presence of leucine and threonine and of a basic substance with some of the properties of an amino acid, as major constituents. The basic substance was later identified with a, y-diaminobutyric acid and isolated from the mixed amino acids of the hydrolysate by precipitation with picric acid, as the DL-picrate (Catch and Jones’). This was the first time that this amino acid, known from the synthetic work of Karrer et S ~ n g e , ~ and Adamson,lo was identified as a constituent of a natural product. This acid has since been shown to be present in hydrolysates prepared under milder conditions as the L-form.ll Receipt of a sample of polymyxin D, the ‘polymyxin’ of Stansly et al.? kindly made available by Dr. Carey of the Lederle Laboratories Division of the American Cyanamid Company, enabled us to identify the same amino acids in this antibiotic, with serine as an additional acid. The optical configuration of the leucine and threonine present in polymyxin A has been determined on the paper chromatogram by an enzymic method (Jones’”). These amino acids were shown to be D-leucine and L-threonine. Subsequent isolation of D-leucine and L-threonine from the hydrolytic products by Catch, Jones, and Wiikinson’l has amply c o n h e d the result obtained by the micro-technique. It was noted early that, when adequate samples of relatively crude polymyxin A were hydrolyzed by acid in sealed tubes, globules of an oily appearance separated from the acid solution and a rancid odor was present. Evaporation of the acid on a steam-bath in an open dish left only a q s t a l line residue. The fatty material was at first discounted as an impurity, but was noted for further study. A private communication from Dr. Malcolm of the Lederle Laboratories Division of the American Cyanamid Company informed us of the presence, in the polymyxin molecule, of a