A team of researchers at Yale University have identified a molecular signal that allows potentially therapeutic proteins to hitch a ride into cells using vesicles, possibly making previously inaccessible proteins vulnerable to drugs.
One of the most daunting challenges facing pharmaceutical scientists today are “undruggable proteins” – the approximately 80% of proteins involved in human disease that do not interact with current drugs. Most drugs today are very small molecules and fit snuggly into relatively deep pockets in a protein, usually to inhibit a chemical reaction. But many proteins involved in disease do not perform chemical reactions. Instead they bind to other proteins, or DNA, or RNA. It has proven extremely difficult to design small molecules that inhibit these binding interactions.
This new discovery of a molecular signal allows therapeutic proteins to hitch a ride into cells using vesicles, or small packets of molecular information that fuse with membranes of cells in a process called endocytosis. The signal helps the protein escape from the vesicle to reach the interior of the cell.