Bakerian lecture - Amino-acid analysis and the structure of proteins

Abstract

In recent years the X-ray crystallographers have made remarkable advances in the interpretation of protein structure, and it is becoming more and more evident that a stage has been reached when their views need to be reconciled with data obtained from accurate amino-acid analysis of the proteins concerned. In all too many cases these data are, unfortunately, not yet available, and the reason why the analyst cannot supply them at short notice is due not so much to the com­plexity of the problem—which he has never sought to minimize—but to the fact that many of the more important methods of analysis in current use are an inheritance from an earlier period when such accuracy as is now demanded would have been considered almost impossible of achievement. From about 1840 until 1900, following the lead given by Liebig and later by Ritthausen, the attention of protein chemists was centred chiefly on the prepara­tion and characterization of various animal and seed proteins; as substances of physiological interest their enzymic digestion products were studied in elaborate detail by Kühne, but little attention was paid to the ultimate decomposition products, the amino-acids, in spite of the fact that Ritthausen as early as 1872 had pointed out that the proportions in which these occur might be characteristic of the protein concerned. The enunciation by Hofmeister and Fischer of the peptide hypothesis in 1901 emphasized for the first time the fundamental importance of the amino-acids, and a most fruitful period followed in which attention became almost exclusively focused on these products. Under the inspiring leadership of Fischer himself great improvements were effected in the separation and identification of the amino-acids, so that by about 1915 reasonably good analyses were available for most of the better-known proteins. Though far from complete, the analytical data showed quite clearly that proteins could differ widely in composition, and in many cases it was possible to correlate composition with nutritive value. Such an aim was, indeed, the incentive behind much of the work of this period.