Vista Lectureship in Organic Chemistry - Eric Kool

The Organic Seminar Series presents: Eric Kool

Vista Chemical Company Regents Endowed Memorial Lectureship in Organic Chemistry

Stanford University 

Host: Eric Anslyn

Title: A Universal Chemical Handle for RNA Biology

Refreshments served at 3:15pm

Location: WEL 2.122

The design and application of small molecule reactive probes is a central theme in chemical biology. In the protein world, simple covalent reactions of electrophiles with amino acid sidechains have revolutionized biology and medicine, giving rise to blockbuster anticancer therapies and enabling screening of interactions in the entire proteome. Here I will describe our efforts to bring analogous chemical strategies to the RNA world.

Our target is the 2’-OH group of RNA, which exists at essentially every position of all transcripts, and is surprisingly reactive for an alcohol in water. I will describe the development of high-yield chemistries for forming covalent bonds with RNA, enabling us to construct ester, carbonate, carbamate, sulfonate and aryl ether linkages. This can be done at nearly every position of an RNA molecule, or can be directed locally to specific nucleotides in a sequence. The chemistry can be permanent, or with careful design can be reversible by reagents or light.

I will describe several ongoing and future applications of this chemistry. Examples include stabilizing RNA therapies, visualizing RNAs in tissues, controlling RNA function, and probing the interaction of small molecule drugs in the living transcriptome.