Enzyme-Instructed Self-Assembly of Small Hexapeptides Based on an Immunoreceptor Tyrosine-Based Inhibitory Motif (ITIM)

DSpace Repository

Show simple item record

dc.contributor.advisor Xu, Bing
dc.contributor.author Yamagata, Natsuko
dc.date.accessioned 2017-06-28T17:37:56Z
dc.date.available 2017-06-28T17:37:56Z
dc.date.issued 2017 en
dc.identifier.uri http://hdl.handle.net/10192/34010
dc.description.abstract Here we show the first example of an immunoreceptor tyrosine-based inhibitory motif (ITIM), LYYYYL, as well as its enantiomeric or retro-inverso peptide, to self-assemble in water upon enzymatic dephosphorylation. In recent years, supramolecular hydrogels that consist of peptidic nanofibrils have attracted considerable attention due to their versatility in biomedical applications. Previous studies discovered that certain short-sequence peptides self-assemble once the phosphate is cleaved by ectophosphatases overexpressed on the surface of cancer cells (enzyme-instructed self-assembly, or EISA). The hydrogels that form upon EISA can be cytotoxic; however, the cytotoxicity of ITIMs has yet to be demonstrated. Upon synthesizing 5 ITIM hexapeptides using standard solid phase peptide synthesis (SPPS), we characterized the resulting hydrogels by transmission electron microscopy (TEM), rheometry and circular dichroism (CD) spectroscopy. We also quantified the dephosphorylation rate of the precursor peptides and examined the effects of stereochemistry on gelation. We examined the cytotoxicity of the peptides on cancer cells by using cell viability assays such as MTT and Live/Dead Cell Viability Assays (2D and 3D). During our study of EISA of the ITIM-based peptides, we unexpectedly observed the moderate cytotoxicities of the L version peptides. This work illustrates a new approach to design bioinspired soft materials from a less explored, but important pool of functional peptides. en
dc.language.iso en en
dc.rights Copyright by Natsuko Yamagata 2017. en
dc.title Enzyme-Instructed Self-Assembly of Small Hexapeptides Based on an Immunoreceptor Tyrosine-Based Inhibitory Motif (ITIM) en
dc.type Thesis
dc.contributor.department Department of Chemistry en


Files in this item

This item appears in the following Collection(s)

Show simple item record

Search the Repository


Browse

My Account

Statistics