Assembly and disassembly of proteins, nature's macromolecules, in response to a specific stimulus is ubiquitous in biology. Mimicking these processes, where proteins are used as the stimulus to disassemble artificial macromolecular assemblies are interesting for a variety of biomedical applications. For example, although targeted drug delivery is not a specific goal for this proposal, the experiments proposed here to obtain the proof-of-concept could have a significant impact in this area. Specifically, this proposal describes the development of versatile strategies to disassemble dendrimer-based amphiphilic assemblies using proteins as stimuli. Facially amphiphilic dendrimers, reported by us recently in the literature, are a unique class of molecules in that these are the only class of amphiphilic dendrimers that form micelle-type assemblies through aggregation. Even more interesting is the fact that these assemblies can be disassembled in response to a stimulus. While stimuli-responsive assemblies themselves have been studied quite extensively, reports where proteins are used as the stimulus for disassembling organized supramolecular assemblies are rather limited. This proposal describes a concerted approach to this problem, which could have broad implications in biology and medicine.
This proposal concerns the design, syntheses, and study of supramolecular assemblies that can be disassembled to release the sequestered guest molecules in response to protein stimuli. Since protein imbalances cause many human diseases, this basic research will have significant implications in biomedicine.
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