Our goal is to facilitate the development of RNA-directed therapies. RNA molecules participate as key players in many biological processes and adopt complex architectures that are required for function. The development of ligands that bind specifically to RNA targets opens exciting new ways to expand greatly the existing repertoire of protein-directed therapeutics.
We focus on four areas of research and apply diverse techniques, including molecular biology, biochemistry, X-ray crystallography, computational chemistry as well as synthetic organic chemistry:
Validation and Screening of New RNA Targets
We use molecular biological and biochemical methods to explore new RNA targets in two therapeutic areas: hepatitis C virus infection (HCV) and cancer. Screening assays are being developed that report on functional consequences of ligand binding to an RNA target in addition to returning binding affinity. (... more)
Structure Determination of RNA Targets and Ligand Complexes
We use X-ray crystallography to investigate the three-dimensional architecture of RNA targets and their complexes with small molecules of both natural and synthetic origin. (... more)
Computational Chemistry of RNA-Ligand Interaction
Structural information from crystallography, along with data from biochemical experiments are combined to investigate in silico the molecular recognition of RNA. We want to develop rules that define RNA-friendly ligands, which will ultimately be applied to the design of novel synthetic ligands.
Design and Synthesis of New Ligands for RNA Targets
Structure-guided design is combined with ligand-based approaches to develop focused small molecule libraries for screening against RNA targets. We develop syntheses for new RNA-friendly molecules of natural product-like complexity. (... more)
