Where are the new drugs? pg. 4
“I see it as a really challenging time. But mostly I see it as a very exciting time.”
Pie in the sky
Another potential source of new drugs: compounds that interact with G-proteins.
G-proteins are intracellular molecular switches, involved in nearly every physiological—and presumably, pathological—process. They translate and transmit signals from the receptor to the “response machinery” deep inside the cell.
Here’s how they work:
Drugs that target GPCRs are rather blunt instruments; they can trigger far-ranging side effects. Is it possible to develop drugs that can be delivered—with “nano-surgical” precision—to the G protein of a specific receptor inside a particular type of cell? Could that achieve the therapeutic manipulation of a unique signaling pathway without affecting physiology anywhere else?
That prospect has tantalized Heidi Hamm, Ph.D., for more than two decades. But until recently the idea was, as Hamm puts it, “total pie in the sky.”
In 1993, Hamm helped solve the structure of the alpha subunit with the late Paul Sigler, M.D., Ph.D., and his colleagues at Yale.
More recently, she and colleagues at the University of Illinois at Chicago and the University of Wisconsin-Madison showed how the beta/gamma subunit of an inhibitory G protein controls the release of neurotransmitters and hormones. It prevents vesicles containing these chemical messengers from fusing to the cell membrane and spilling their contents outside the cell.