Bacterial infection emerged as a public health threat recently and it is urgent and important to develop an effective approach to counter the drug resistant bacteria. One promising approach is multi/polyvalency - multiple simultaneous bindings between two biological entitles. In this thesis, I report our recent work on using multivalency approach against vancomycin resistant enterococci (VRE). We used both rigid metallic and organic linkers to dimerize vancomycin, and the resulting divalent vancomycin showed a improvement in minimum inhibition concentration (MIC) values (0.25 ~ 1 μg / mL) compared with vancomycin itself (0.128 ~ 1 mg / mL) and other dimers or oligomers of vancomycins linked by pure organic, flexible linkers. These results indicate that combining rigid linkers with vanco...[ Read more ]

Bacterial infection emerged as a public health threat recently and it is urgent and important to develop an effective approach to counter the drug resistant bacteria. One promising approach is multi/polyvalency - multiple simultaneous bindings between two biological entitles. In this thesis, I report our recent work on using multivalency approach against vancomycin resistant enterococci (VRE). We used both rigid metallic and organic linkers to dimerize vancomycin, and the resulting divalent vancomycin showed a improvement in minimum inhibition concentration (MIC) values (0.25 ~ 1 μg / mL) compared with vancomycin itself (0.128 ~ 1 mg / mL) and other dimers or oligomers of vancomycins linked by pure organic, flexible linkers. These results indicate that combining rigid linkers with vancomycin will offer a promise method to explore the multi/polyvalency and develop potent antibiotics based on existing clinical drugs.