FINDING the right drug could become as easy as sitting back and letting
evolution take its course. Chemists in the US say they have automated a process
that makes a mixed bag of molecules evolve into just one type, the 鈥渇ittest鈥� for
binding to a chosen target molecule.
Many chemists are pinning their hopes for new drug design on combinatorial
chemistry, which involves creating a 鈥渓ibrary鈥� of hundreds or thousands of
molecules and finding out which one sticks to a target molecule in the desired
way. But testing the myriad molecules to see which works is time-consuming.
Now Alexey Eliseev and Marina Nelen, chemists at the University of Buffalo in
New York, have demonstrated a way to turn the chemical library into a 鈥渉abitat鈥�
where only the successful molecules survive. They used different forms of the
molecule methylguanidium, which can arrange itself in three ways with respect to
its rigid double bonds.
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First, they passed a mixture of the three molecules over a substrate of
target molecules, to which only one of the methylguanidium shapes could bind.
The remaining molecules were carried on to a chamber where they were zapped with
ultraviolet light. This randomly changed or 鈥渕utated鈥� the methylguanidium
molecules from one shape to another, creating more of the 鈥渇it鈥� binding
molecules.
Repeating this process over and over again eventually 鈥渒illed off鈥� all the
poorly binding molecules, while all the tightly binding ones were trapped, the
researchers say in Chemistry: A European Journal (vol 4, p 825). A
quick rinse with a solvent freed the evolved molecules from the substrate.
鈥淚t鈥檚 very useful for discovering how molecules bond,鈥� says Benjamin Miller,
a chemist at the University of Rochester in New York. 鈥淭he field is really
exploding.鈥� He hopes similar techniques will eventually be used to produce
drugs.
