Inhibitors of protein biosynthesis

Abstract

The process of protein synthesis, in which the information encoded by the four-letter alphabet of nucleic acid bases is translated into defined sequences of amino acids linked by peptide bonds, is an exquisitely complex process involving more than 100 macromolecules. Amino-acid- specific transfer RNA (tRNA) molecules, messenger RNAs (mRNAs) and many soluble proteins are required, in addition to the numerous proteins and three types of RNA that comprise the ribosomes. Although many general features of the protein synthetic machinery are similar in prokaryotic and eukaryotic organisms, a number of naturally occurring compounds specifically inhibit bacterial protein synthesis and thereby provide us with therapeutic agents of considerable value. Intriguingly, ‘nature’ has been much more successful in producing compounds that discriminate between bacterial and mammalian protein synthesis than synthetic organic chemistry. No wholly synthetic compound capable of specific inhibition of bacterial protein synthesis has yet emerged from organic chemistry laboratories. Inhibitors specific for protein synthesis in fungi are as yet unknown, probably because the similarities between the mechanisms in fungal and mammalian cells are too close to permit this degree of discrimination.