Professor Ronald T. Raines, Massachusetts Institute of Technology, Department of Chemistry
ABSTRACT: 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 conversion of 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.