Corante

About this Author
DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

Chemistry and Drug Data: Drugbank
Emolecules
ChemSpider
Chempedia Lab
Synthetic Pages
Organic Chemistry Portal
PubChem
Not Voodoo
DailyMed
Druglib
Clinicaltrials.gov

Chemistry and Pharma Blogs:
Org Prep Daily
The Haystack
Kilomentor
A New Merck, Reviewed
Liberal Arts Chemistry
Electron Pusher
All Things Metathesis
C&E News Blogs
Chemiotics II
Chemical Space
Noel O'Blog
In Vivo Blog
Terra Sigilatta
BBSRC/Douglas Kell
ChemBark
Realizations in Biostatistics
Chemjobber
Pharmalot
ChemSpider Blog
Pharmagossip
Med-Chemist
Organic Chem - Education & Industry
Pharma Strategy Blog
No Name No Slogan
Practical Fragments
SimBioSys
The Curious Wavefunction
Natural Product Man
Fragment Literature
Chemistry World Blog
Synthetic Nature
Chemistry Blog
Synthesizing Ideas
Business|Bytes|Genes|Molecules
Eye on FDA
Chemical Forums
Depth-First
Symyx Blog
Sceptical Chymist
Lamentations on Chemistry
Computational Organic Chemistry
Mining Drugs
Henry Rzepa


Science Blogs and News:
Bad Science
The Loom
Uncertain Principles
Fierce Biotech
Blogs for Industry
Omics! Omics!
Young Female Scientist
Notional Slurry
Nobel Intent
SciTech Daily
Science Blog
FuturePundit
Aetiology
Gene Expression (I)
Gene Expression (II)
Sciencebase
Pharyngula
Adventures in Ethics and Science
Transterrestrial Musings
Slashdot Science
Cosmic Variance
Biology News Net


Medical Blogs
DB's Medical Rants
Science-Based Medicine
GruntDoc
Respectful Insolence
Diabetes Mine


Economics and Business
Marginal Revolution
The Volokh Conspiracy
Knowledge Problem


Politics / Current Events
Virginia Postrel
Instapundit
Belmont Club
Mickey Kaus


Belles Lettres
Uncouth Reflections
Arts and Letters Daily
In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« The Details of the Baucus Bill | Main | Which Pfizer / Wyeth Sites Will Close? »

September 28, 2009

Chew On This, Enzyme

Email This Entry

Posted by Derek

File this one under "Department of Odd Ideas". There's a paper coming out in JACS that has a neat variation on an idea that's been kicking around for some years now: molecularly-imprinted polymers (MIPs). A MIP is a sort of molded form around some molecular template - you make your polymer in the presence of the desired target molecule, with the idea that you'll then form target-shaped cavities in the resulting gel.

These things have been worked on for years in the analytical chemistry field, since they have the potential to form very robust sensors for a wide variety of substances. The thought has also been that they might serve as pseudo-enzymatic catalysts for some reactions as well, although I get the impressions that that's been harder to realize. From the outside, the whole area seems to be one of those that goes on for years as something that's still developing and hasn't quite taken off.
MIP%20abstract%20scheme.jpg
This latest idea may or may not change that, but it's ingenious. What this group (from two French labs) has done is anchor the initiation point of the polymer to an enzyme inhibitor molecule - in this case, to an amidine inhibitor of trypsin. The resulting polymer turns out to have strong inhibitory activity for the enzyme, about a thousandfold higher than the starting amidine - as well it might, if it's muffling the active site like a huge beach towel. They tried a number of potential polymeric systems, settling on some neutral methacrylates, since charged species didn't seem to give binding (or specificity) at all.

The control experiments support their interpretation of what's going on. The resulting polymers don't seem to recognize (or inhibit) a variety of otherwise similar proteins. If control polymers are formed without the anchoring group, they have no inhibitory effect. Similarly, if the experiment is done with an excess of non-polymerizable inhibitor, the effect goes away as well (since the active site is already occupied).

I'm not sure that these things will find much use as enzyme inhibitors in living systems, unless you're looking to shut down some sort of enzyme in the gut. (In that case, you might be able to give someone a glass full of soluble polymeric stuff, with the expectation that it wouldn't be absorbed and would emerge more or less unchanged. But perhaps there are applications under blood filtration or dialysis conditions, or topical ones. At any rate, it's a neat idea which is now looking for a home. . .

Comments (3) + TrackBacks (0) | Category: Chemical News


COMMENTS

1. SP on September 28, 2009 8:30 AM writes...

That seems pretty similar to JM Lehn's dynamic combinatorial chemistry- reversibly assemble inhibitor fragments in the presence of the target molecule, then lock them down once equilibrated and you'll come out with the active ones pasted together. It's pretty limited since the reversible aqueous-compatible reactions were mostly imine formation followed by reduction, but they've had some successful examples.

Permalink to Comment

2. philip on September 29, 2009 10:01 AM writes...

The idea of molecular imprinting has always been an attractive one because the practice of reproducing things on a macro scale using molds works so well. The problem is that when the unit size of the materials building the mold gets close to the size of the features you're trying to imprint, it all breaks down. Imagine building a mold for a hand by fusing grains of sand. Not so hard. Try it with BB's and it still works. Use marbles and it sort of becomes like abstract art. Baseballs and it starts getting weird. Most of this type of work is like trying to make a mold of a hand with grapefruits. Occasionally it looks intriguing, but it will never be universally applicable. It's why antibodies like big things and the all the early nanotechnology stuff was nonsense.

Permalink to Comment

3. Paul on September 30, 2009 4:25 PM writes...

I've wondered if molecular imprinting might have been going on back when life was getting started. It might have been a useful mechanism for making random blobs of junk have directed catalytic properties. The behavior you'd want to find would be "polymerize in the presence of X makes the stuff catalyze the production of X", where X is some relevant amino acid, etc.

Permalink to Comment

POST A COMMENT




Remember Me?



EMAIL THIS ENTRY TO A FRIEND

Email this entry to:

Your email address:

Message (optional):




RELATED ENTRIES
What If?
Novartis Impresses Where Others Have Failed
Exelixis Against the Wall
A Last Summer Day Off
The Early FDA
Drug Repurposing
The Smallest Drugs
Life Is Too Short For Some Journal Feeds