International Collaboration in Chemistry: Exploring the interactions between small molecules and biopolymers using localized surface plasmon resonance (LSPR) spectroscopy

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With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Yitzhak Tor from the University of California, San Diego, to explore the interactions between small molecules and large biopolymers and cell surface components, using gold island-based localized plasmon transducers, as part of an International Collaboration in Chemistry. As a proof-of-concept, this label-free method will be used to assess the affinity and selectivity of aminoglycoside antibiotics and their derivatives to the ribosomal decoding site RNA, a key recognition event that lowers the fidelity of protein biosynthesis. This system has been selected due to its fundamental significance, as it illustrates the fact that low molecular weight ligands are capable of meddling with a critical function of a large biological machine. The proposed research will shed light on the molecular features that govern the selectivity of the ligands selectivity toward the bacterial RNA, when compared to the human competing targets. Furthermore, advancing the proposed platform technology will facilitate a convenient, label-free exploration of diverse macromolecular recognition events where low molecular weight ligands influence the folding and function of key macromolecules. Small molecules are capable of interfering with the function of critical cellular components, such as the ribosome, where all proteins are synthesized. To learn about the molecular interactions involved, a new technology based on a specialized optical technique will be advanced, where the biological targets do not need to be modified or altered. In this fashion, information about the interaction of small molecules with diverse biological targets can be accumulated rapidly. This pursuit will allow graduate students and postdoctoral fellows to acquire training in diverse scientific disciplines, ranging from synthetic techniques to surface chemistry. This project will also be integrated into an outreach program to introduce high school students at the UCSD Preuss School to basic principles of chemistry and biology. Simple lab experiments and demonstrations will be developed to illustrate the process of modifying surfaces by self-assembling ?designer? molecules and monitoring biorecognition events using straightforward optical instrumentation.