Executive Summary : | NSAIDs are commonly used to reduce joint pain, stiffness, inflammation, and body aches. Amphiphilic molecules are designed and synthesized to construct nanostructures for various applications, including enzymatic catalysis, 3D printing, sensing, drug delivery, wound healing, antibacterial, and anti-inflammatory therapy. Fluorinated molecules are known for their therapeutic applications, with their fluorous effect enhancing lipophilicity, improved metabolic stability, and increased binding efficacy to target protein molecules. These molecules also exhibit antimicrobial properties by inhibiting cyclooxygenase-2 (COX-2) activity. The rational design of the project includes N-terminus aromatic capping, fluorous effect for COX-2 inhibition and microbial infection, and peptidase stability using D-amino acids. The NSAID oxaprozin is used to protect the N-terminal of self-assembling peptides, hypothesizing that the protected peptide could inhibit COX-2-mediated inflammation by inhibiting prostaglandin biosynthesis. The designed peptides contain D-amino acids, which are protease stable, increasing the bioavailability of molecules and increasing antimicrobial and anti-inflammatory activity. The incorporation of fluorine into the self-assembling peptides could provide fluorous effect by increasing lipophilicity, stability, and polarity of molecules. The proposed research project will be divided into four major parts: synthesis of various dipeptides and their intermediates, hydrogel preparation and optimization of rheological properties, performance of biological activity of dipeptides, and the development of a robust and economical process for self-assembling materials synthesis. |