Tuesday, October 25, 2011

10 Unsolved Science Mysteries (part 9) : Can We Devise New Ways to Create Drugs?

     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.



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