New antibiotic species formed in crosslinking polymyxin B to linear gramicidin Dubos

Abstract

Crosslinking of a mixture of 1,3,5-tri-carbobenzoxy polymyxin B and desformylgramicidin using 4,4'-difluoro-3,3'-dinitrodiphenylsulphone(FNPS) at pH 10.5 results in the formation of three species of intermolecularly crosslinked products. The decarbobenzoxylated products are (polymyxin B) sub(2), polymyxin B-(desformylgramicidin) sub(2) and (desformylgramidicin) sub(2). The first product is isolated in very poor yield (5-10%), the second in 16-30% and the last product in 24-43% yield, respectively, under different experimental conditions of crosslinking. Addition of FNPS to a mixture of tri-carbobenzoxy polymyxin B and desformylgramicidin (1:2,25) favoured maximum yield (30%) of polymyxin B-(desformylgramicidin) sub(2). (Desformyl-gramicidin) sub(2) was the predominant product when desformylgramicidin was added after FNPS addition to tri-carbobenzoxy polymyxin B. The observation reveals possibilities of producing crosslinked antibiotics with tailor-made spectra of activity. However, the polymyxin B-(desformylgramicidin) sub(2) isolated by the authors is possessed of only lower levels of activity, relative to gramicidin and polymyxin B.