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Deep Cavitands for Molecular Recognition in Biomimetic Membrane Environments

  • Author(s): Perez, Lizeth
  • Advisor(s): Hooley, Richard J
  • et al.
Creative Commons 'BY' version 4.0 license
Abstract

The cell’s surface is complex and multicomponent in nature. It is the setting where a variety of crucial life processes take place, mediated by the interaction of cell surface receptors with specific molecules outside of the cell. Studying how particular interactions take place in this convoluted environment can be difficult in actual cell membranes. Modeling components of the cell’s surface can be beneficial in studying cellular processes, although mimicking these systems poses a substantial challenge. Synthetic receptors such as calix[n]arenes, cyclophanes, and cyclodextrins are capable of performing molecular recognition of ionic and hydrophobic guests in aqueous environments, however, these synthetic receptors are not useful for molecular recognition studies in membrane environments.

This work studies the molecular recognition abilities of water-soluble deep cavitands in membrane environments. The binding behavior of cavitands in membrane-like envrionments was studied using NMR analysis. The differences in binding behavior were elucidated in lipid environments compared to free solution. Supported lipid bilayers have been previously employed to mimic membrane environments, and the binding of trimethylammonium-tagged compounds and cationic native proteins were monitored via surface plasmon resonance (SPR) spectroscopy. By varying the functionality at the cavitand’s rim, a broader range of interactions were explored. The binding of anionic native proteins was possible by positioning a positive charge at the rim of the cavitand and more complex interactions between host and guest were possible by tailoring guests that utilize dual mode binding. In order to imitate larger structures on cell surfaces such as glycopolymers, cavitand-mediated atom transfer radical polymerization (ATRP) was performed in order to create a functional polymer on the SLB surface. Utilizing aminoethyl methacrylate, an amine polymer was formed that can be further derivatized by reacting fluorescent compounds for visualization, or epitopes for the adhesion of larger biomolecules such as avidin. The versatility of the amine-functionalized polymer was demonstrated with its ability to bind large structures such as cells at the interface of SLBs. The diverse interactions of the variably functionalized cavitands also led to their use in indicator displacement assays (IDA) for sensing a variety of analytes ranging from post translational modifications to metals and steroids.

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