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Synthesis and Antibiotic Activity of Vitamin B12-Vancomycin Conjugates

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Dissertation is embargoed till 30 November 2025(3.12 MB)

Date

2023

Authors

Stackpole, Ben

Supervisor

Brasch, Nicola
Seale, Brent

Item type

Dissertation

Degree name

Bachelor of Science (Honours)

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Publisher

Auckland University of Technology

Abstract

Vitamin B12 has the potential to be used as a “Trojan horse” for drug delivery applications, with previously reported examples including anti-cancer drugs and antimicrobial drugs. As B12 is too large to cross cellular membranes by diffusion, humans and bacteria uptake it via active transport processes mediated by a series of proteins. Conjugating therapeutic molecules to B12 allows this process to be hijacked to transport cargo into cells. Because B12 is an essential nutrient and many species of bacteria cannot synthesise it themselves, this is a promising method for transporting antibiotics into bacteria. This may be especially useful in the case of Gram-negative bacteria, which possess an additional outer membrane that prevents many antibiotics from entering the cell. In this research project, we investigated the antibiotic activity of B12-vancomycin conjugates. Vancomycin is a glycopeptide antibiotic which inihibits bacterial cell wall synthesis. Due to its large size, it cannot diffuse across bacterial membranes and so it is only effective against Gram-positive bacteria. By conjugating vancomycin to B¬12, we hypothesised that it could be transported across the outer membrane of Gram-negative bacteria and inhibit their growth. Four different B12-vancomycin conjugates were successfully synthesised, differing in the linker used and the site of conjugation to B12. The conjugates were tested for antibiotic activity against Escherichia coli. None of the conjugates displayed antibiotic activity.

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http://hdl.handle.net/10292/17019

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Bachelor with Honours Dissertations - open access