Chemistry on Supramolecular Nanostructures: Peptide Amphiphiles with Non-Covalent or Covalent-Linking Funcationality

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In this work several self-assembling PA systems containing covalent-linking functionalities have been investigated. These covalently linkable PAs were designed to probe the supramolecular structure by covalent capture of the nanofibers and also improve the mechanical stiffness of the gel-material. The diacetylene motif was the main functional group investigated because of its topochemical reaction and colorimetric change as a useful indicator of polymerization. The syntheses, characterization and application of diacetylene PAs are discussed in Chapter 3. These molecules were observed to successfully polymerize, turning an intense blue color suggesting there is ordering within the nanofibers, while still maintaining its nanofiber morphology. Varying PA molecules change the PDA spectroscopic signal, suggesting differences in PA packing within a nanofiber. It was possible therefore to characterize molecular packing differences within a nanofiber using the PDA as a colorimetric probe. By oscillatory rheology, gels that were polymerized showed increased stiffness. Because of their enhanced stiffness, it was possible to microfabricate for the first time patterned structures in PA-based materials, performed by Dr. Alvaro Mata. Another photo-reactive functional group, coumarin, was chosen for its reversible chemical reaction and potential biological use as an anti-cell proliferative agent. Photoirradiation reactions of the coumarin PA system were not found to be 100% reversible regardless of where the coumarin molecule was synthetically placed on the PA. SKBr-3 breast cancer cells were cultured in a coumarin PA-coated well to investigate the PA's potential anti-proliferative effects. Compared to free 7-hydroxycoumarin, coumarin PAs show at least a 5-fold increase in cytotoxicity compared to free coumarin. Another chemical strategy to build larger macroassemblies from the bottom-up is to include noncovalent interactions located at the periphery of the PA nanofibers. For this purpose PAs containing the nucleobases (adenine or thymine) were synthesized without covalent-linking functionality. Nucleobase interaction was observed by CD spectroscopy including adeninethymine base-pairing when mixing the two complementary PAs. Microscopy of the PAs as individual or mixed systems showed significant bundling of the nanofibers. These nucleobase PA systems could be developed for further applications as oligonucleotide binding agents. Nucleobase PAs were found to interact with polyadenylic acid (PolyA). Microscopy of the thymine PA and the PolyA mixture also showed bumpy fiber morphologies, suggesting that the biopolymer may be wrapping itself around the individual nanofibers.

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  • 10/02/2018
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