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

Chun, Taewoo; Pattem, Jacob; Gillis, Richard B.; Dinu, Vlad T.; Yakubov, Gleb E.; Corfield, Anthony P.; Harding, Stephen E.

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 (M1 = 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 s20, w = ~ 4.65 S. The intrinsic viscosity [η] was found to be (3.2 ± 0.1) mL/g: both this, the value for s20,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.

Citation

Chun, T., Pattem, J., Gillis, R. B., Dinu, V. T., Yakubov, G. E., Corfield, A. P., & Harding, S. E. (2023). Self-association of the glycopeptide antibiotic teicoplanin A2 in aqueous solution studied by molecular hydrodynamics. Scientific Reports, 13(1), Article 1969. https://doi.org/10.1038/s41598-023-28740-8

• Journal Article Type: Article
• Acceptance Date: Jan 24, 2023
• Online Publication Date: Feb 3, 2023
• Publication Date: Feb 3, 2023
• Deposit Date: Apr 15, 2023
• Publicly Available Date: Apr 18, 2023
• Journal: Scientific Reports
• Electronic ISSN: 2045-2322
• Publisher: Springer Science and Business Media LLC
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 1
• Article Number: 1969
• DOI: https://doi.org/10.1038/s41598-023-28740-8
• Public URL: https://nottingham-repository.worktribe.com/output/17071718
• Publisher URL: https://www.nature.com/articles/s41598-023-28740-8#citeas
• Additional Information: Received: 31 October 2022; Accepted: 24 January 2023; First Online: 3 February 2023; : The authors declare no competing interests.