Self-association of the glycopeptide antibiotic teicoplanin A2 in aqueous solution studied by molecular hydrodynamics

Abstract

Abstract The natural glycopeptide antibiotic teicoplanin is used for the treatment of serious Gram-positive related bacterial infections and can be administered intravenously, intramuscularly, topically (ocular infections), or orally. It has also been considered for targeting viral infection by SARS-CoV-2. The hydrodynamic properties of teicoplanin A2 (M 1 = 1880 g/mol) were examined in phosphate chloride buffer (pH 6.8, I = 0.10 M) using sedimentation velocity and sedimentation equilibrium in the analytical ultracentrifuge together with capillary (rolling ball) viscometry. In the concentration range, 0–10 mg/mL teicoplanin A2 was found to self-associate plateauing > 1 mg/mL to give a molar mass of (35,400 ± 1000) g/mol corresponding to ~ (19 ± 1) mers, with a sedimentation coefficient s 20, w = ~ 4.65 S. The intrinsic viscosity [ $$\eta$$ η ] was found to be (3.2 ± 0.1) mL/g: both this, the value for s 20,w and the hydrodynamic radius from dynamic light scattering are consistent with a globular macromolecular assembly, with a swelling ratio through dynamic hydration processes of ~ 2.