Mar 25, 2015 – NMR Topical Group Meeting

Biomacromolecules constitute an important segment of pharmaceuticals and exhibit an increasing percentage in pipelines, and play crucial roles in the drug research and development.  Many categories of pharmaceutically interesting molecules have been comprehensively characterized in my research, including antimicrobial drugs and peptides, antiviral drug for influenza A infection, ion channels and amyloid fibrils, using multidimensional Solid-State NMR (SSNMR). Their chemical and biophysical properties of SSNMR interest include structure, aggregation, drug-water, drug-membrane, and drug-protein interactions. My research goal is to investigate these properties and correlate such valuable structural and dynamic information with their pharmaceutical and biological functions to uncover the underlying mechanisms.

In this talk, I’ll take a few examples to illustrate the role of SSNMR in the characterization of these drugs, membrane-active peptides and ion channels. In particular, I’ll show how ¹³C, ¹⁵N, ¹⁹F and ³¹P NMR can be successfully utilized to characterize many natural abundant drug molecules. Domain interactions studied by ¹H spin diffusion and NMR relaxation will also be discussed. These examples will include the antimicrobial mechanism of a drug in clinical trial, inhibition of the replication of influenza A virus, and the mechanism of an antimicrobial peptide that shows double gram selectivity. In addition, resent structural findings of ion channels, i.e. voltage gated ion channels (Kv and VDAC), will be discussed. In these examples, I’ll discuss a few cutting-edge SSNMR techniques including ¹H-detection at ultra-fast spinning and signal enhancement by dynamic nuclear polarization (DNP), and their potential impact on drug characterization.