STRUCTURAL CHARACTERIZATION OF GLYCOPEPTIDE ANTIBIOTICS RELATED TO VANCOMYCIN BY FAST ATOM BOMBARDMENT MASS SPECTROMETRY

Abstract

A series of glycopeptide antibiotics related to the vancomycin-ristocetin family have been successfully analyzed by fast atom bombardment mass spectrometry (FABMS). The FAB mass spectra of glycopeptides weighing up to 2, 100 daltons exhibit intense molecular ions and fragment ions from which information concerning carbohydrate composition and sequence are readily obtained. Careful adjustment of the FABMS experimental conditions has enabled the accurate masses of the glycopeptides to be determined by high resolution FABMS with an accuracy of better than six ppm. Comparison of the observed molecular ion cluster pattern with calculated isotope distributions reveals the precise number of chlorine atoms in these molecules, which, together with the accurate mass data, can be used to restrict the number of possible elemental compositions to a meaningfully small value. These techniques have been used to characterize several glycopeptides of known structure including ristocetin, actinoidin, avoparcin, vancomycin and A35512B, as well as aridicins A, B and C which are three new, novel members of the vancomycin class.