Leveraging selective peptoid degradation for biosensing applications

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McKenzie, Hattie Christine (Schunk)

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Development of multi-functional materials and biosensors that can achieve an in-situ response designed by the user is a current need in the biomaterials field, especially in complex biological environments, such as inflammation, where multiple enzymatic and oxidative signals are present. In the past decade, there has been extensive research and development of materials chemistries for detecting and monitoring enzymatic activity, as well as for releasing therapeutic and diagnostic agents in regions undergoing oxidative stress. However, there has been limited development of materials in the context of enzymatic and oxidative triggers together, despite their closely tied and overlapping mechanisms. One major fundamental design challenge to integrating multiple sensing elements in tandem is instability and uncontrolled cross-reactivity. Thus, to successfully detect biomarkers in synergy, there is need for innovative strategies in controlling biostability while maintaining well-defined bioactivity. We aim to address this challenge using synthetic, sequence-defined peptoids. Due to their N-substitution, peptoids are generally regarded as resistant to biological degradation, such as enzymatic and hydrolytic mechanisms. This stability is an especially attractive feature for therapeutic development and is a selling point of many previous biological studies. However, oxidative degradation of peptoids mediated by reactive oxygen and nitrogen species (ROS/RNS) is key mode of degradation that remains to be fully explored. ROS and RNS are biologically relevant in numerous contexts where biomaterials may be present, thus, improving understanding of peptoid oxidative susceptibility is crucial to exploit their full potential in the biomaterials field. Toward this end, we demonstrate a fundamental characterization of sequence-defined peptoid chains in the presence of chemically generated ROS, as compared to ROS-susceptible peptides such as proline and lysine oligomers. These results expand understanding of peptoid degradation to oxidative and enzymatic mechanisms, and demonstrate the potential for peptoid incorporation into materials where selectivity towards oxidative degradation is necessary, or directed enzymatic susceptibility is desired. By considering the materials chemistry of enzymatically and oxidatively triggered biomaterials in tandem, we hope to encourage synthesis of new biosensors that capitalize on their synergistic roles and overlapping mechanisms in inflammatory environments for future applications in disease diagnosis and monitoring.


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