Dr. Jonathan Greer

"Mapping a drug target is sort of like finding Cinderella's slipper," says Jonathan Greer, director of the structural biology group for Abbott's pharmaceutical products division."It lets us see what we're trying to fix, then we've got to find the right foot."

In this "mapping" process, scientists often use a technique known as X-ray crystallography.They begin by growing crystals of identically ordered protein molecules.By firing a high-powered x-ray beam through the crystal protein, scientist can determine the molecule's diffraction pattern, how x-rays are scattered through the crystal.They then analyze this pattern by computer and use it to render the 3-D image of the protein.

Jonathan Greer , Abbott Laboratories

Lecture 12QSAR in Drug Research
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Jonathan Greer , Abbott Laboratories

Seminar 3Lead Structure Development

Jonathan Greer, Abbott Laboratories

Just ask Jonathan Greer, head of structural biology at Abbott Laboratories in North Chicago, Ill.He describes how one team of researchers at the company spent years studying a single candidate for a cancer drug.
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"We went from being a goat to being heroes in five days," Greer says.The drug is now being tested in animal studies.

SPOTTING SIDE EFFECTS.

Structure-based drug design played a large role in the discovery and optimization of an inhibitor of the anti-apoptotic proto-oncogene Bcl that is planned to begin Phase I studies sometime in 2006, says Jonathan Greer, Ph.D., director, structural biology, advanced technology, global pharmaceutical R&D, Abbott Labs.

The company employed its SARbyNMR technology, screening approximately 10,000 fragments (250 Da or smaller) by NMR to identify weak binders to a desirable protein target, explains Dr. Greer.When two fragments are identified that bind to appropriate, adjacent sites on the target, each one can be optimized separately and then linked together.Once connected, the two fragments get the benefit of binding to two adjacent sites and become a potent, viable lead.

The rationale for SARbyNMR is that screeners can tap into vast chemical diversity without physically screening several million compounds.Structure-based drug design was also instrumental in optimizing other properties beyond potency in Abbotts Bcl-2 inhibitor, says Dr. Greer.

Jonathan Greer, Ph.D., Director, Structural Biology, Abbott Laboratories

Dr. Jonathan Greer, Ph.D. University of Cambridge
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Dr. Jonathan Greer received his BA in Chemistry/Bio-Chemistry from Princeton University and his Ph.D in Structural Biology from University of Cambridge.He served o­n the faculty of Columbia University for ten years and is currently Director of Structural Biology at Abbot Labs.