Enzyme-Instructed Self-Assembly (EISA) of Small Molecules Inhibits Cancer Cells

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dc.contributor.advisor Xu, Bing
dc.contributor.author Li, Jie
dc.date.accessioned 2018-09-17T15:43:45Z
dc.date.available 2018-09-17T15:43:45Z
dc.date.issued 2018
dc.identifier.uri https://hdl.handle.net/10192/35924
dc.description.abstract As an important class of catalysts that exhibit high efficiency and specificity in cellular environment, enzymes control various signaling cascades of biological systems. Self-assembly, a process that autonomously reorganizes components also plays important roles in maintaining the cell integrity and functions. Enzyme instructed self-assembly is a process that integrates enzymatic transformation and molecular self-assembly. That is, an enzyme catalyzes the conversion of a precursor to a molecule that self-assembles in aqueous solution, which usually results in hydrogelation. In this thesis, we discuss how enzymes trigger supramolecular self-assembly of small molecules to form hydrogels and the relevant applications. As a multi-step molecular process, enzyme mediated self-assembly is able to take place pericellularly, intracellularly, in vitro, or in vivo. Various enzymes, such as phosphatases, esterases, β-lactamases, and thermolysins, can catalyze the process. Here I describe some of my works on enzyme instructed self-assembly, which show promising applications in tissue engineering and cancer therapy. The expression levels of enzymes may vary depending on the types of cells, tissues, or organs, so the utilization of enzymes can control the response of the self-assembly according to the biological environment. Thus, enzyme instructed self-assembly promises new applications in biomedicine since the integration of the inherent enzymatic reactions with self-assembly achieves excellent spatiotemporal control. Besides enzyme instructed self-assembly, the development of supramolecular chemistry has inspired researchers to explore more properties of self-assemblies. Chapter 5 describes the application of aromatic-aromatic interactions to reconsititute the original secondary structures of isolated peptides which originated from proteins. The simply conjugation of aromatic motifs to the isolated peptides can successfully restore their secondary structure which may lead to more applications. Chapter 7 talks about the work that we used supramolecular self-assemblies to explore how the stability of peptides in biological environment and the proteolysis of these peptides affect the activities of the peptide nanofibers against cancer cells. These works indicate that there can be more applications of supramolecular self-assemblies in chemical or biological fields.
dc.description.sponsorship Brandeis University, Graduate School of Arts and Sciences
dc.format.mimetype application/pdf
dc.language English
dc.language.iso eng
dc.publisher Brandeis University
dc.relation.ispartofseries Brandeis University Theses and Dissertations
dc.rights Copyright by Jie Li 2018.
dc.subject self-assemble
dc.subject supramolecular hydrogel
dc.subject anti-cancer
dc.subject enzyme
dc.subject cytotoxicity
dc.title Enzyme-Instructed Self-Assembly (EISA) of Small Molecules Inhibits Cancer Cells
dc.type Thesis
dc.contributor.department Department of Chemistry
dc.degree.name PhD
dc.degree.level Doctoral
dc.degree.discipline Chemistry
dc.degree.grantor Brandeis University, Graduate School of Arts and Sciences


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