The lipid bilayer that encases human cells has evolved to keep the outside out, and the inside in. This barrier is not, however, impenetrable. Some small molecules, including many drugs, can burrow through and manifest therapeutic activities. Others can be “cloaked” to endow membrane permeability, and then uncloaked inside cells. We have learned how to beneficially cloak proteins, which are typically 100-fold larger than small-molecule drugs. Specifically, the use of tuned diazo compounds to convert protein carboxyl groups into esters enables a protein to traverse the lipid bilayer. The nascent esters are substrates for endogenous esterases that regenerate native proteins within cells. The ability to deliver native proteins directly into cells opens a new frontier for molecular medicine.
Professor Raines (he/him) received Sc.B. degrees in chemistry and biology at MIT, performing undergraduate research with Christopher T. Walsh. He received A.M. and Ph.D. degrees in chemistry at Harvard University for research done with Jeremy R. Knowles. He was a Helen Hay Whitney postdoctoral fellow with William J. Rutter in the Department of Biochemistry and Biophysics at the University of California, San Francisco. He then joined the faculty at the University of Wisconsin–Madison, where he became the Henry Lardy Professor of Biochemistry, Linus Pauling Professor of Chemical Biology, and a Professor of Chemistry. He was a Visiting Associate in Chemistry at Caltech in 2009. In 2017, he returned to MIT as the Roger and Georges Firmenich Professor of Natural Products Chemistry, an Extramural Member of the Koch Institute for Integrative Cancer Research at MIT, and an Associate Member of the Broad Institute of MIT and Harvard.
Professor Raines is an author of over 400 peer-reviewed journal articles, and an inventor on more than 60 US patents. He has advised over 100 graduate students and postdoctorates. Alumni from his research group enjoy careers as faculty members at distinguished research universities, medical schools, and colleges; and as research scientists at innovative start-up companies, leading corporations, and government laboratories.