January 4, 2005

Cool Bio-Tech toys - Inteins

Derek Lowe at In The Pipeline has an article on something that I have never heard of before but sounds like a very cool new tool for biochemistry: bq. Tadpoles to the Rescue? Speaking of odd ideas that might have applications in drug discovery, there's an interesting one in the latest issue of Nature Methods (2, 31). A group at the Molecular Sciences Institute in Berkeley reports a new way to detect and quantify molecular binding targets. And if you think that this sounds like something we're interested in over here in the drug discovery business, you are correct-o-matic. bq. This idea piggybacks, as you might expect, on the mighty king of detection and quantification in molecular biology, PCR. The ability to hugely amplify small amounts of DNA is unique, the biochemical equivalent of a photomultiplier , and many people have taken advantage of it. In this case, they also make ingenious use of weird beasts called inteins, about which a great deal of background can be found here. Briefly, inteins are sort of DNA parasites. They insert into genes and are read off into an extraneous stretch of protein in the middle of the normal gene product. But then they quickly clip themselves out of the protein - they have their own built-in cut-and-splice mechanism - and leave the originally intended protein behind them, none the worse for wear. Derek goes on to tall about one of the very practical applications of this work: bq. The paper demonstrates this in several different systems, going all the way up to a real-world example with blood serum. What's impressive about the technique is that it seems to work as well as antibody methods like ELISA. Getting a good reliable antibody is no joke, but these folks can make smaller proteins with much worse intrinsic affinity perform just as well. And if you turn around and do the trick starting with an antibody, you can increase the sensitivity of the assay by orders of magnitude. And you get a real quantitative readout, with about +/- 10% accuracy. To give you the most startling example, the authors were able to detect as few as 150 single molecules of labeled bovine serum albumin in a test system. Considering the way that progress works for stuff like this, you will see a portable room-temperature tester for most diseases (Stock and Human -- imagine a quick reliable test for BSE or Avian Flu) as well as for very small amounts of specific chemicals. As Derek said, this piggybacks off PCR. The developer of PCR (Kary B. Mullis) got the Nobel for his work - interesting to see if these people get the prize as well... A wonderful book by Dr. Mullis is Dancing Naked in the Mind Field Posted by DaveH at January 4, 2005 8:55 PM