Bacitracin properties

The field of peptide synthesis is never far removed from the study of natural products, many of which exhibit peptide and peptidomimetic structures. It is fitting that this treatise be concluded with a section on the synthesis of key peptide-based natural products. Section 16 commences with the synthesis of bacitracin)30 a cyclic peptide with antibiotic properties. The synthesis of this target structure is carried out in solution and by solid-phase chemistry. The molecule contains a lactam-bridged cyclic heptapeptide with a pendent tripeptide (Section 16.1.1). An elegant route to the synthesis of the thiazoline building block is included. 

A number of zinc compounds with organic constituents (e.g., zinc salts of organic acids) have therapeutic uses. These include antidandruff zinc pyridinethione, antifungal zinc undecylenate used to treat athlete s foot, zinc stearate and palmitate (zinc soap), and antibacterial zinc bacitracin. Zinc naphthenate is used as a low-toxicity wood preservative, and zinc phenolsulfonate has insecticidal properties and was once used as an intestinal antiseptic. The inhalation of zinc soaps by infants has been known to cause acute fatal pneumonitis characterized by lung lesions similar to, but more serious than, those caused by talc. Zinc pyridine thione (zinc 2-pyridinethiol-l-oxide) has been shown to cause retinal detachment and blindness in dogs this is an apparently species-specific effect because laboratory tests at the same and even much higher dosages in monkeys and rodents do not show the same effect. 

Methods of Production, Concentration and Partial Purification, with a Summary of theChemical Properties of Crude Bacitracin. J. Bact. SS, 249 (1948). 

Properties White to gray-brown powder. Slight unpleasant odor, less bitter than bacitracin. Soluble in water, pyridine, ethanol less soluble in acetone, ether, chloroform, benzene pH of saturated aqueous soluble 3.5-5.0. Available also as the sodium salt. 

Properties Creamy-white powder. Almost insoluble in water. Good thermal stability, usually has 50-60 units/mg of bacitracin activity. 

In 1945, a new antibiotic was reported it was produced by a grampositive sporulating bacillus of the B. subtilis group and isolated from cultures of contaminated tissue removed from a fracture of the tibia. This strain was named after the patient Tracey I and the active principle in the cell-free filtrates of broth cultures was therefore called Bacitracin . The antibiotic was first produced in surface cultures Ass a d later by submerged cultures in synthetic media A94. Later the organism was classified as a strain of B. licheniformis. In 1949 another antibiotic from a strain of B. licheniformis, originally called A-5, was described under the name ayfivin A6 . It soon became apparent that bacitracin and ayfivin were closely related in their physical, chemical and biological properties " . The name ayfivin was therefore abandoned in favour of bacitracin . 

This structure, although consistent with many facts, did not explain the peculiar properties of the A-terminal isoleucine and the negative test for —SH groups. Further experiments led to the conclusion that a thiazoline ring is formed between isoleucine and cysteine this was later proved to be correct. All these results led to the formula for bacitracin A which is now generally accepted - Figure 1.4). 

Bacitracin-cellulose is an efficient affinity adsorbent for isolation of proteolytic enzymes. Its flow properties stability, and the possibility of a repeated use make it a promising adsorbent for large-scale operations. 

Guy Newton, who had come from Cambridge to Oxford as a doctoral student after a distinguished war record, then joined in a study of cephalosporin N. Our interest in this substance derived at first from the finding that some of its properties were those of a labile peptide, for we were already working on the thiazoline-containing peptide, bacitracin. By the end of 1953, cephalosporin N had been shown to be a new penicillin with a 8-(D-a-aminoadipyl) side chain, and it was later renamed penicillin N. It then seemed to us that an uncharacterized antibiotic named synnematin, which had been obtained in a crude form at the Michigan Department of Health from culture filtrates of Cephalosporium salmosynnematum, might be identical to penicillin N, and a direct com-... 

Anker, H. S., B. A. Johnson, J. Goldberg, and F. L. Meleney Bacitracin methods of production, concentration, and partial purification, with a summary of the chemical properties of crude bacitracin. J. Bacteriol. 55, 249 (1948). 

Paramagnetic metals have been used to investigate the structure-conformation properties of peptides, as exemplified by studies on bacitracin. Transition metal ions seem to enhance the antimicrobial activity of bacitracin. The peptide is thought to have a conformation in which the penta-peptide tail folds over the seven-membered peptide ring (Galardy et a/., 1971). A further conformational feature is proposed where the carbonyl carbon of the phenylalanyl residue is proximal to the free amino terminal group of isoleucine. 

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