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Polypeptide Materials with Engineered Functionalities

  • Author(s): Negri Jimenez, Graciela E.
  • Advisor(s): Deming, Timothy J
  • et al.

Polypeptide materials were developed to address a variety of biomedical applications, including tissue engineering and drug delivery. This work was focused on increasing the pool of amino acid monomers to further the functionality and manipulation of polypeptide materials. This dissertation describes the development of polypeptide materials with stimuli-responsive behaviors and new functionality.

A boronic acid-functionalized polypeptide-PEG copolymer was synthesized. This copolymer demonstrated the ability to reversibly bind to glycosylated enzymes; formed stable complexes at pH 7.4, and dissociated at pH 5.0, the pH of a lysosomal compartment. This complexation was specific to glycosylated enzymes and the boronic acid functionality used. These results suggest potential application of these copolymers in enzyme replacement therapies.

A new L-lysine based -amino acid N-carboxyanhydride (NCA) monomer was synthesized in order to prepare photodegradable polypeptide hydrogels. The lysine derivative was caged using a UV-labile protecting group. Hydrogels were assembled using this residue as the hydrophobic block. Material properties could be adjusted by variation of hydrophobic block length and composition, as well as polymer concentration in water. These parameters were also used to tune the degradation profile of these hydrogels upon exposure to 365 nm light. Loading of dyes into these networks followed by irradiation demonstrated the ability for these gels to encapsulate and facilitate the triggered release of therapeutics.

Finally, polysulfonium-based polypeptide hydrogels were synthesized, assembled and characterized using unnatural amino acid NCA monomers. Creation of these new materials relied on application of previously reported post-polymerization thioether alkylation methodology from the Deming lab to new building blocks. The resulting polymers were found to tolerate a range of functionality without loss of hydrogel properties. While hydrophobic block length and polymer concentration were used to tune gel properties, the choice of alkylating agent was also responsible for changing gel stiffness. Use of mixtures of different alkylating agents led to further fine adjustment of materials properties. The incorporation of azide groups was also tolerated by the scaffolds, and this functionality was used for subsequent click chemistry to demonstrate the retention of gel properties even after further functionalization. This methodology has implications for the incorporation of fluorescent labels or cell attachment-promoting ligands.

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