Rational Design of Helical Peptoids for Tetracycline Conjugation: Insights into Molecular Complexation Mechanisms

This work addresses the need for cost-effective, stable, and sensitive detection of tetracycline, which is a widely used antibiotic molecule, with environmental and health risks associated with its incorrect use. We explored the use of N-substituted polyglycine oligomers (peptoids) as molecules capable of tetracycline conjugation. Peptoids are readily synthesized by solid-phase synthesis, offering great chemical diversity and enhanced stability. Inspired by a short aptamer that selectively binds tetracycline, we designed helical peptoids containing side chains selected for their ability to promote π-π stacking interactions and hydrogen bonding. Five peptoid sequences were selected, differing in monomer order, and their complexation capacity was investigated by using different mass spectrometric techniques and circular dichroism. Tandem mass spectrometry and ion mobility spectrometry investigations confirmed the complex formation between peptoids and tetracycline. Additionally, circular dichroism revealed that the peptoid sequence influences the complexation. Our findings demonstrate the potential for rationally designed peptoids as capture probes for sensing applications.