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whiskey in the jar
The core business of chemistry is a practical, creative one: making molecules, a key to creating everything from new materials to new antibiotics that can outstrip the rise of resistant bacteria. In the 1990s one big hope was combinatorial chemistry, in which thousands of new molecules are made by a random assembly of building blocks and then screened to identify those that do a job well.
Once hailed as the future of medicinal chemistry, “combi-chem” fell from fa-vor because it produced little of any use. But combinatorial chemistry could enjoy a brighter second phase. It seems likely to work only if you can make a wide enough range of molecules and find good ways of picking out the minuscule amounts of successful ones. Biotechnology might help here—for example, each molecule could be linked to a DNA-based “bar code” that both identifies it and aids its extraction. Or researchers can progressively refine the library of candidate molecules by using a kind of Darwinian evolution in the test tube.
They can encode potential protein-based drug molecules in DNA and then use error-prone replication to generate new variants of the successful ones, thereby finding improvements with each round of replication and selection. Other new techniques draw on nature’s mastery at uniting molecular fragments in prescribed arrangements. Proteins, for example, have a precise sequence of ami-no acids because that sequence is spelled out by the genes that encode the proteins.
Using this model, future chemists might program molecules to assemble autonomously. The approach has the advantage of being “green” in that it reduces the un-wanted by-products typical of traditional chemical manufacturing and the associated waste of energy and materials. David Liu of Harvard University and his co-workers are pursuing this approach. They tagged the building blocks with short DNA strands that program the linker’s structure. They also created a molecule that walks along that DNA, reading its codes and sequentially attaching small molecules to the building block to make the linker—a process analogous to protein synthesis in cells. Liu’s method could be a handy way to tailor new drugs. “Many molecular life scientists believe that macromolecules will play an increasingly central, if not dominant, role in the future of therapeutics,” Liu says.
Using this model, future chemists might program molecules to assemble autonomously. The approach has the advantage of being “green” in that it reduces the un-wanted by-products typical of traditional chemical manufacturing and the associated waste of energy and materials. David Liu of Harvard University and his co-workers are pursuing this approach. They tagged the building blocks with short DNA strands that program the linker’s structure. They also created a molecule that walks along that DNA, reading its codes and sequentially attaching small molecules to the building block to make the linker—a process analogous to protein synthesis in cells. Liu’s method could be a handy way to tailor new drugs. “Many molecular life scientists believe that macromolecules will play an increasingly central, if not dominant, role in the future of therapeutics,” Liu says.
SOURCE : SCIENTIFIC AMERICAN MAGAZINE OCTOBER 2011
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