Advancing Bioorthogonal Tetrazine Reactions

Tuesday, April 19, 2016 - 2:00pm
Fung Auditorium | Powell-Focht Bioengineering Hall
Neal Devaraj, Ph.D.

Assistant Professor of Chemistry and Biochemistry

University of California, San Diego

Advancing Bioorthogonal Tetrazine Reactions

We are developing novel bioorthogonal reactions as tools for addressing problems in biological imaging and bottom up synthetic biology.  Recently we have developed and implemented synthetic methods to synthesize novel tetrazines with improved stability, as well as small methyl-cyclopropene dienophile coupling partners.  The latter compounds enable the use of tetrazine cycloadditions for imaging and labeling applications that require small probes, for instance in metabolic imaging.  We have implemented cyclopropenes to track the distribution of lipid analogs in live mammalian cells using fluorogenic tetrazine imaging probes.  Additionally, we have recently synthesized sugar analogs containing methyl-cyclopropenes, enabling metabolic imaging of glycan synthesis in live cells.  Importantly, this technique can be done sequentially with classic “click” chemistry approaches, enabling multicolor imaging of 2 different metabolically incorporated molecules.

Neal K. Devaraj is an Assistant Professor of Chemistry and Biochemistry at the University of California, San Diego (UCSD). He received a dual BS in Chemistry and Biology from the Massachusetts Institute of Technology, where he performed undergraduate research with Moungi G. Bawendi. He subsequently obtained a PhD in Chemistry from Stanford University under James P. Collman and Christopher E. D. Chidsey. During his time at Stanford, Neal explored the use of copper catalyzed cycloadditions on electrode surfaces and studied the role of electron transfer rates on the multielectron reduction of oxygen by porphyrin electrocatalysts. Following this, Neal moved to the Harvard Medical School where he worked with Ralph Weissleder on developing tetrazine cycloadditions for biomedical applications such as cellular imaging of small therapeutics and in-vivo imaging of disease related biomarkers. In 2010 he was promoted to the rank of Instructor at the Harvard Medical School as an NIH Career Development Fellow. In 2011 he moved to the UCSD where his laboratory is developing bioorthogonal reactions as tools in imaging and synthetic biology.