METODO PARA PURIFICAR COMPUESTOS ANTIBIOTICOS DE LA FAMILIA DE DALBAHEPTIDOS MEDIANTE CENTRADO ISOELECTRICO (CI) EN UN ELECTROLIZADOS MULTICOMPARTIMENTAL CON MEMBRANAS DE INMOVILINAS, EN PARTICULAR MEMBRANAS ZWITTERIONICAS. UN OBJETIVO ADICIONAL DE LA INVENCION SON LOS COMPUESTOS ANTIBIOTICOS PUROS QUE PUEDEN OBTENERSE DE ACUERDO CON EL PRESENTE PROCESO, EN PARTICULAR EL DERIVADO 6 SUP,B} - DESCARBOXI - 6 SUP,B} - (HIDROXIMETIL) N SUP,63} - 3 - (DIMETILAMINO)PROPILAMIDA PURO DEL ANTIBIOTICO A40926.

A42867 is a new glycopeptide antibiotic of the ristocetin-vancomycin class active against aerobic and anaerobic Gram-positive bacteria. A42867 is produced by a strain of Nocardia nov. sp. ATCC 53492. A42867 was isolated during a screening program aimed at the discovery of new members of this glycopeptide class of antibiotics, by affinity chromatography based on an acyl-D-alanyl-D-alanine probe. The structure of A42867 was elucidated by fast atom bombardment MS, high field 2D 1H NMR spectroscopy, and HPLC analysis of the hydrolyzed carbohydrates. A42867 differs from vancomycin in the sugar portion and in the presence of only one chlorine atom in the peptide core. Its biological activity on Gram-positive aerobic and anaerobic bacteria is similar to that of other antibiotics of this group.

A40926 antibiotics are new glycopeptides which are much more active than other members of this class against Neisseria gonorrhoeae. Their activity against Gram-positive bacteria, including coagulase-negative Staphylococci, is similar to that of other glycopeptides. An A40926 preparation containing factors A and B ("A40926 A + B complex") was hydrolyzed to the aglycone and to the mannosyl and N-acylaminoglucuronyl aglycones. The mannosyl aglycone and the aglycone were less active than A40926 A + B complex against Streptococci and Gram-positive anaerobes and lost the anti-gonorrheal activity. In contrast, the N-acylaminoglucuronyl aglycones were as active as the parent complex against these Gram-positive bacteria and were moderately active against N. gonorrhoeae. The aglycone and, even more so, the N-acylaminoglucuronyl aglycones, had better activity than the parent complex against coagulase-negative Staphylococci. In experimental septicemia in the mouse, A40926 A + B complex and its derivatives had activity proportional to their MIC for the test organism.

A simple HPLC method for quali- and quantitative determination of teicoplanin and A40926 in fermentation broths and in biological fluids is described. The sample is purified on affinity chromatography and then analyzed on a reverse phase column using a gradient phosphate buffer-acetonitrile as mobile phase and UV detection at 254 nm. No interference from endogenous sources has been observed. The analytical method, with partial modifications, was also used to isolate on semipreparative scale the single components of these antibiotics, in order to investigate their structure and their biological activity.