UC Berkeley

Supramolecular chemistry is a diverse field that encompasses host-guest interactions, mechanical bond formation, metal coordination, and other noncovalent chemistries. The design strategies of supramolecular chemistry have been implemented in a diverse set of applications, but has seen limited use in the field of chemical biology. By combining supramolecular chemistry with chemical biology, new discoveries and advances could be made that would not be possible without a supramolecular approach. This work therefore sought to combine supramolecular strategies and chemical biology for applications in protein modification and nanomedicine. By using cucurbituril host-guest chemistry, a supramolecular-promoted copper-free click chemistry reaction was developed for protein modification. Cucurbituril host-guest chemistry was additionally explored as a selective protecting group for either the N terminus in the case of cucurbit[7]uril (CB7), or as a lysine protecting group in the case of cucurbit[6]uril (CB6). Supramolecular interactions were further utilized in the design of new turn-on diagnostic probes for 129Xe NMR/MRI detection of cancer, via the rotaxane-mediated suppression, and subsequent activation of Xe-CB6 host-guest interactions. Lastly, self-assembled protein-based nanomaterials were explored for applications in chemotherapeutic drug delivery to glioblastomas, with a special focus on how the morphology of protein-based nanomaterials can affect their biodistributions and drug delivery efficacies. Throughout this work, supramolecular interactions are interwoven with applications and techniques in chemical biology to achieve new advances that would not be possible otherwise.