Isolation and structure determination of Pachybasium cerebrosides which potentiate the antifungal activity of aculeacin.

A set of four cerebrosides was isolated from a Pachybasium species and purified by preparative reversed-phase HPLC. All four products displayed activity in a natural product screen aimed at detecting novel cell wall-active antifungal agents based on synergy with the known glucan synthetase inhibitor, aculeacin. Based on degradation studies, fast atom bombardment mass spectrometry and 13C and high field 1H NMR techniques, the structure of the major cerebroside was determined to be (4E,8E)-N-D-2'-hydroxy-(E)-3'- hexadecenoyl-1-O-beta-D-glucopyranosyl-9-methyl-4,8-sphingadiene. The other components were found to be the corresponding 2'-hydroxypalmitic acid analog with one less double bond and an analogous pair containing 2'-hydroxystearic acid with and without the 3' double bond.

Structural characterization of glycopeptide antibiotics related to vancomycin by fast atom bombardment mass spectrometry.

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.

Synthesis and characterization of iodinated vasopressin antagonists which retain high affinity for the vasopressin receptor.

The mono- and di-iodinated analogs of lysine and arginine vasopressin have been prepared previously but not well characterized chemically. Their biological activities are greatly reduced with respect to LVP or AVP. In this paper we report a convenient synthesis of iodinated AVP agonists and antagonists, their purification by high performance liquid chromatography, and their characterization by fast atom bombardment mass spectrometry. In contrast to the results obtained with agonists, the mono-iodinated vasopressin antagonist retains virtually the full receptor activity of its non-iodinated parent. This should allow the preparation of labeled vasopressin antagonists of high specific activity for receptor characterization and isolation.