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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: Twitter: Dereklowe

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« EMBL Chemical Biology: Natural Product Leads | Main | EMBL Chemical Biology: Covalent Probes »

September 26, 2012

EMBL Chemical Biology: Weird Aggregating Compounds

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Posted by Derek

Now I'm listening to Jim Wells (UCSF) talk about (among other things) this work, where they found a compound aggregating and causing activity in their assays. But this one wasn't doing the standard globular gunk that the usual aggregation gives you. Instead, the compound formed nanofibrils - microns long. And the enzyme that the compound showed activity against turns out to bind to the surface of the fribrils. Wells likens the effect to the way that Brussel sprouts grow, and his electron micrograph does indeed look pretty close. The question is, does this mimic something that happens "in real life", or is it a complete artifact? There's a paper in press in JBC going into some of the details. Just goes to show you that compounds are capable of doing things that you'd never have been able to guess.

Comments (6) + TrackBacks (0) | Category: Chemical Biology


1. lynn on September 26, 2012 5:11 PM writes...

If not ontogeny recapitulates phylogeny, then chemistry recapitulates Brussels sprouts. I'm liking your ongoing meeting abstracts, Derek.

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2. Fries With That? on September 26, 2012 8:09 PM writes...

Complete artifact. Lipstick on a pig.

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3. Inefficient Reaction on September 27, 2012 9:23 AM writes...

Jim Wells removes those tags on mattresses!

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4. Anonymous on September 27, 2012 9:51 AM writes...

It is disturbing that Wells published a science paper to claim a hit molecule that works as a monomeric ligand, then published another one in JACS to retract the claim in the Science paper. HTS fooled many people. I am not sure Wells's result is reproducible.

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5. UmemployedMedChemist on September 27, 2012 12:29 PM writes...

The association of the enzymes on nanofibrils brings up all sorts of potential applications for protein drug delivery. Factor VIII or ADA comes quickly to mind. It could be a replacement for PEGylated protein delivery.

I'm sure Dr. Wells has had the incredible smart foresight to consider such obvious applications.

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6. Anonymous on September 27, 2012 10:37 PM writes...

Considering that Wells own data showed these so-called NanoFibrils kill every cell they are sprinkled on, probably not such a great idea for protein delivery. A company called Calithera was founded on the Science paper results, strangely, Wells and Calithera do not seem to be associated with each other anymore.

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