1 Polypeptide Antibiotics of Medicinal Interest

Abstract

Publisher Summary This chapter discusses that since the discovery of tyrothricin—the first peptide antibiotic isolated—more than a hundred antibiotic substances containing one or more amino acids or moieties derived from amino acids have been described. However, despite considerable efforts, the structures of relatively few peptide antibiotics have been determined and ultimately proved by synthesis. There are several reasons for this. First, many of these antibiotics, after their discovery, characterization, and evaluation, were not of sufficient practical importance and work on them was discontinued. Second, they have relatively complicated structures. Unlike the peptide hormones, which are composed of a limited number of natural amino acids found in proteins, many peptide antibiotics contain a large variety of components other than amino acids. Besides the frequently occurring amino acids not isolated from proteins many other components, such as hydroxy acids, amino sugars, fatty acids, and pyrimidine derivatives are also present. They also often contain unusual peptide linkages, unknown in proteins. Furthermore, most of the peptide antibiotics are of cyclic nature and for this reason are resistant to enzymatic attack, which makes their structural elucidation in many instances more complicated. A third reason for this lack of knowledge may be the present limited therapeutic importance of the peptide antibiotics, mainly as a result of their narrow antimicrobial spectrum and their relatively high toxicity. However, the recent increase in serious infections caused by gram-negative bacteria and their growing resistance to the broad spectrum antibiotics has shifted focus to some of the peptide antibiotics, which are the most active inhibitors of these organisms.