Date of Graduation
Master of Science in Chemical Engineering (MSChE)
Second Committee Member
Biotherapeutic, Green Chemistry, Peptoid, protein
Biotherapeutic drugs, derived from biological molecules such as proteins and DNA, are becoming an integral and exceptionally critical aspect of modern medicine. Compared to common pharmaceutical drugs, biotherapeutics are much larger in size and have greater target specificity, allowing them to treat many chronic diseases ranging from cancer to rheumatoid arthritis. The major issue with protein based therapeutics is that they readily undergo proteolysis, or enzymatic degradation, when administered through subcutaneous injections. Traditionally, biotherapeutic modification procedures have centered on the use of PEG derivatives. This process, called PEGylation, is unfavorable due to the increases in molecular weights of the proteins and the heterogeneous mixture of products formed. Instead of PEG derivatives, we propose peptoids with N- methoxyethylglycine (NMEG) side chains to decrease proteolysis. NMEG groups are more advantageous than PEG derivatives due to their low molecular weight and ability to form homogeneous products. Our work focuses on increasing the protease resistance of target biotherapeutic proteins by cross-linking a NMEG-5 peptoid to a cytochrome c via reductive amination. In the presence of a reducing agent, an imine bond is formed through the reduction of the peptoid’s aldehyde group and cytochrome c’s primary amine groups. Due to the expensive and unstable nature of commercially available aldehyde side chains, a green chemistry method, using only sodium hypochlorite (bleach) and 2,6,6-Tetramethylpiperidinoxy (TEMPO, free radical), oxidized the peptoid’s hydroxyl group into the desired aldehyde for cross linkage.
Roberts, J. L. (2017). Green Chemistry Oxidative Modification of Peptoids Utilizing Bleach and TEMPO. Graduate Theses and Dissertations Retrieved from https://scholarworks.uark.edu/etd/2581