Yale team develops drug-targeting method for once-untouchable proteins
Yale University researchers have figured out a way that may enable drug design to target the nearly 80% of all proteins involved in human disease deemed as "undruggable," or unable to interact with existing drugs on the market.
Details are published in the latest edition of the journal Chemistry & Biology. But the short version is this: The research team led by Alanna Schepartz spotted a crucial molecular signal that enables proteins that are potentially therapeutic to enter cells by way of vesicles, or small packets of molecular data that fuse with cell membranes through endocytosis. Once the signal is issued, as the researchers explain, the protein can escape from the vesicle and reach the cell interior. Schepartz said in a statement that understanding this mechanism and how it works gives scientists a shot to engineer molecules to take a particular, prescribed pathway into a cell.
This could be a huge shot in the arm for drug discovery and development work. As the researchers note, most drugs on the market are very small molecules. They fit pretty tightly as well, into relatively deep protein pockets in order to perform their function--inhibiting a chemical reaction. But that function ignores many other proteins that don't perform any chemical reaction that are also involved in a disease. Their role, the scientists explain, is simply to bind to RNA, DNA, or other proteins. And researchers have struggled to design small molecule drugs that address this behavior and block the binding process.
While some proteins are used as drugs, they also operate outside the cell, not inside of it where the disease processes can truly be targeted at their point of origin. And so this process, if successful, could give drug developers an effective way to target a disease more regularly deep at its source.
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