Bioactive peptide analogs: In vivo and in vitro production

Abstract

The first peptide antibiotics discovered and introduced were penicillin, gramicidin S, and tyrocidine [1–2]. Although a decade ago it was suggested that peptide antibiotics would decline in importance, we have since seen the steady development of already known compounds as well as the discovery of new ones; thus, the unforeseen rise of cyclosporins, produced by Beauveria nivea. This cycloundecapeptide entered immunosuppressor screening as an antifungal, and has now become an essential compound in organ transplantations [4,5]. Bleomycin, a modified glycooctapeptide isolated from Streptomyces verticillus, was developed by biotransformation to second and third generation cytostatics peplomycin and liblomycin [6]. In the search for new antibacterial compounds, the introduction of new sensitive screening methods has led to many promising structures. Analogs of vancomycin, modified glycoheptapeptides, have been detected in many actinomycetes by their unique property of binding to the D-alanyl-D-alanine tail of growing murein [7, 8]; many of their complex structures have now been elucidated, and several are being developed as antibacterial agents. Screenings directed at the β-lactam structure led to new β-lactams produced by unusual bacteria [9], the discovery of monobactams [10] with the fast introduction of the synthetic aztreonam, and the surprising finding that γ-lactones attach to penicillin binding proteins [11–14].