The small molecule hinokitiol transports iron across cell membranes where transport proteins are missing. Credit: Julie McMahon and Liz Ahlberg Touchstone, University of Illinois
“If you’re sick because you have too much protein function, in many cases we can do something about it. But if you’re sick because you’re missing a protein that does an essential function, we struggle to do anything other than treat the symptoms. It’s a huge unmet medical need,” said Burke, who also is a medical doctor. Burke’s team found that a small molecule called hinokitiol, derived from a species of cypress tree found in Japan, can transport iron across cell membranes that are missing transport proteins.
In a healthy system, transport proteins move iron across cell membranes to uptake iron from the gut or make hemoglobin for red blood cells. But when the transport protein is missing, iron can’t cross the membrane, causing anemia. The researchers found that three hinokitiol molecules can wrap around an iron atom and transport it directly across the membrane where the missing protein should be.
The researchers tested hinokitiol in mice, rats and zebrafish that were missing iron-transport proteins. They found that orally administered hinokitiol restored iron uptake in the guts of mice and rats, and that simply adding it to the tank of anemic zebrafish prompted hemoglobin production. They also found that it restored iron transport in human cells taken from the lining of the gut.
Next, Burke’s group hopes to find more small molecules that can function as molecular prosthetics for other diseases caused by protein deficiencies, with a particular focus on cystic fibrosis. “These findings suggest that replacing missing proteins with molecular-scale prosthetics may represent a general way to think about treating a wide range of human diseases that have thus far remained out of reach with traditional medicine,” Burke said. The National Institutes of Health and the Howard Hughes Medical Institute supported this work. https://medicalxpress.com/news/2017-05-molecular-prosthetics-proteins-disease.html http://science.sciencemag.org/content/356/6338/608
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