Use of Capillary Electrophoresis to Measure Dimerization of Glycopeptide Antibiotics

Abstract

Capillary electrophoretic methods were used to examine dimerization and estimate dimerization constants (Kdim) for the glycopeptide antibiotics vancomycin, ristocetin A, and LY264826 (A82846B). TheKdimfor LY264826 was 60- and 200-fold higher than theKdimfor ristocetin A and vancomycin, respectively. Dimerization of vancomycin measured in the presence of the cell wall analogN,N′-diacetyl-L-Lys-D-Ala-D-Ala was enhanced 200-fold; however, dimerization of ristocetin A was antagonized by the presence ofN,N′-diacetyl-L-Lys-D-Ala-D-Ala. The relative differences inKdimdetermined by capillary electrophoresis in general follow the same trend as those observed using nuclear magnetic resonance spectroscopy and sedimentation equilibrium.