Reactive polymer enables efficient in vivo bioorthogonal chemistry
- Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114
-
Edited by David A. Tirrell, California Institute of Technology, Pasadena, CA, and approved January 31, 2012 (received for review August 16, 2011)
Abstract
There has been intense interest in the development of selective bioorthogonal reactions or “click” chemistry that can proceed in live animals. Until now however, most reactions still require vast surpluses of reactants because of steep temporal and spatial concentration gradients. Using computational modeling and design of pharmacokinetically optimized reactants, we have developed a predictable method for efficient in vivo click reactions. Specifically, we show that polymer modified tetrazines (PMT) are a key enabler for in vivo bioorthogonal chemistry based on the very fast and catalyst-free [4 + 2] tetrazine/trans-cyclooctene cycloaddition. Using fluorescent PMT for cellular resolution and 18F labeled PMT for whole animal imaging, we show that cancer cell epitopes can be easily reacted in vivo. This generic strategy should help guide the design of future chemistries and find widespread use for different in vivo bioorthogonal applications, particularly in the biomedical sciences.
Footnotes
-
↵1N.K.D. and G.M.T. contributed equally to this work.
- ↵2To whom correspondence should be addressed. E-mail: rweissleder{at}mgh.harvard.edu.
-
Author contributions: N.K.D., G.M.T., and R.W. designed research; N.K.D., G.M.T., E.J.K., and B.M. performed research; E.J.K. contributed new reagents/analytic tools; N.K.D., G.M.T., and R.W. analyzed data; and N.K.D., G.M.T., and R.W. wrote the paper.
-
The authors declare no conflict of interest.
-
This article is a PNAS Direct Submission.
-
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1113466109/-/DCSupplemental.
