The pharmaceutical companies would find small compounds that mimic the effects of protein drugs still escape breakdown in the gut. Now scientists have taken the first step in uncovering a small molecule that plays such a turn in mice. The new compound, described in tomorrow Science , mimics the action of a protein that triggers the growth of white blood cells
Many protein drugs. - Including insulin and other hormones known cytokines- -Stick ideal for large areas on their receivers. This makes researchers fear that small chemicals - that could be just 2% the size of a protein - were too puny to run on these receptors. But there was hope: When cytokines bind to their receptors, they drag receptors together into pairs called dimers. This aggregation seems to be what turns on a receiver, and small molecules, such as a peptide, may well be able to do the trick.
A Ligand Pharmaceuticals research team in San Diego and SmithKline Beecham Pharmaceuticals Collegeville and King of Prussia, Pennsylvania, wanted to find a block of granulocyte-colony-stimulating factor (G-CSF), which is commonly used to stimulate the immune system of patients after chemotherapy. To accelerate research, the team designed a mouse cell line to test the activity of G-CSF-like. When G-CSF activates its receptor, it activates ultimately STAT proteins called; the cell engineering team to increase the generation of light protein luciferase, which would be activated by STAT molecules. The researchers then treated mouse cells with thousands of compounds and taken to those who made the cells glow. They hit on a small organic compound called SB 247464 which stimulated growth mouse white blood cells in culture and in live mice.
Although SB 247 464 does not work with human cells, the discovery will stimulate pharmaceutical research of protein drugs mimicking said Mark Goldsmith, who studies cytokine receptors at the University of California, San Francisco. He suggests, adding that small molecules, "we can imitate many interactions it a few years ago would have expected to be much more difficult."
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