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Bundle-Forming α-Helical Peptide-Dendron Hybrids

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dc.contributor.advisor Rudick, Jonathan G en_US
dc.contributor.author Marine, Jeannette Elizabeth en_US
dc.contributor.other Department of Chemistry en_US
dc.date.accessioned 2017-09-20T16:51:46Z
dc.date.available 2017-09-20T16:51:46Z
dc.date.issued 2016-12-01 en_US
dc.identifier.uri http://hdl.handle.net/11401/77046 en_US
dc.description 144 pgs en_US
dc.description.abstract Accurate control over the three-dimensional arrangement of atoms in synthetic materials remains a challenge for polymer and supramolecular chemistry. A defined sequence of monomers programs the folding and self-assembly of peptides and proteins, which makes them excellent candidates for materials in which the precise arrangement of atoms is known. The inherent sensitivity of peptides to external stimuli hampers their practical application. Conjugating peptides with synthetic polymers creates biohybrid materials with increased stability and processability. Hybrid biomaterials can retain the folding and self-assembly properties of peptides. Our approach to hybrid biomaterials is to combine helix bundle-forming peptides with a class of structurally perfect polymers called dendrons. These novel peptide-dendron hybrids offer unprecedented control over folding and self-assembly in synthetic materials. A general synthetic strategy was required to prepare peptides with reactive groups to participate in copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. Assembling peptides with hydrophobic amino acids bearing azides and alkynes resulted in difficult sequences. Therefore, an alternative strategy was developed whereby polar lysine residues were used in the assembly of peptides and later transformed to azidonorleucine residues. The quantitative nature of the diazotransfer reaction with imidazole-1-sulfonyl azide (ISA) was demonstrated through MALDI-TOF and HPLC experiments. This strategy was effective both in solution and on solid-phase to transform large numbers of lysines in a peptide. Orthogonally protected lysines provided a method to site-specifically transform lysine residues on-resin. The reactivity and versatility of the diazotransfer reaction provides a general strategy to site-specifically incorporate multiple azides after chain assembly. The CuAAC reaction is a bioorthogonal reaction that introduces a small 1,4-triazole linkage to conjugate the dendrons to the peptides in a graft-to manner. Iterative synthesis was used to prepare sequence-defined peptides and second-generation dendrons resulting in monodisperse starting materials. Monodisperse and defect-free products were obtained from CuAAC reactions of dendrons with peptides. The monodisperse nature of the peptide-dendron hybrids was confirmed using MALDI-TOF and HPLC. The first examples of peptide-dendron hybrids that fold and self-assemble into α-helical bundles have been designed on the basis of hydrophobic patterning of the amino acid sequence. The α-helical secondary structure of the hybrids, which was found to be dependent on the concentration of the hybrid and the ionic strength of the solution, was confirmed from circular dichroism (CD) spectroscopy experiments. Titration studies demonstrated that the hybrids self-assemble into bundles of α-helices with the dendrons on the outside of the bundle. Characterization of several bundle-forming α-helical peptide dendron hybrids has provided initial principles to design synthetic materials that display the structure and function of native peptides. en_US
dc.description.sponsorship This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. en_US
dc.format Monograph en_US
dc.format.medium Electronic Resource en_US
dc.language.iso en_US en_US
dc.publisher The Graduate School, Stony Brook University: Stony Brook, NY. en_US
dc.subject.lcsh Organic chemistry -- Polymer chemistry -- Chemistry en_US
dc.subject.other Biohybrid materials, Dendrons, Peptide, Self-assembly en_US
dc.title Bundle-Forming α-Helical Peptide-Dendron Hybrids en_US
dc.type Dissertation en_US
dc.mimetype Application/PDF en_US

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