Real Chemistry

I had little to do last night, so I decided to download Stumble Upon for Firefox.  While I was stumbling, I came across an outstanding video that teaches and reinforces the underlying principles of chemical reactions. If I had this type of tutorial when I was an undergraduate, I might very well have become a chemist rather than a biologist!

 

Until next time….

Good Luck and Good Reactions!!!!!!!

 

 

GFP Finally Gets Its Due

 As you may have heard, three scientists Osamu Shimomura, Martin Chalfie and Roger Tsien shared this year’s Nobel Prize in chemistry for their pioneering work on the Green Florescent Protein (GFP). GFP revolutionized the fields of molecular biology and cell biology and led to a greater understanding of the roles of proteins in cell, physiology, development and molecular trafficking.

I first became acquainted with GFP back in the mid 1990s when I was working in Bill Ward’s laboratory at Rutgers University. Bill had worked on GFP for over 25 years and I convinced him that GFP would be an ideal educational tool to teach biochemistry and molecular biology to undergraduate students. Prior to my arrival in Bill’s lab, a couple of graduate students had created so-called, “brightness” GFP mutants using molecular evolution techniques that were en vogue at the time. Because they were much brighter than wild type GFP, I used these mutants to develop laboratory exercises that showcased the principles of protein purification, polyacrylamide gel electrophoresis and molecular cloning.  Although I published a paper on my work, it was the pioneering work of Ron Mardigian at BioRad that ultimately led to the development in 1997 of GFP-based education kits. Ron’s GFP kits were a huge success and are now used to teach biochemistry and molecular biology at the high school and college levels throughout the world.

GFP is an effective educational tool because everyone including children and adults is fascinated by things that glow. This brings to mind something that happened at a global GFP conference that Bill Ward organized in 1997 at Rutgers University. There were over 300 GFP researchers from all over the world in attendance. Bill, who is something of character and has a flair for the dramatic, wanted to WOW the conference attendees. Prior to the meeting, Bill asked us to prepare 2 liters of bacteria that over expressed the GFP “brightness” mutant. During the opening session of the conference, Bill had the 2 liter flask (sitting on a UV lamp) at the podium with him. The room was very dark (on purpose) and without warning he switched on the lamp—I will never forget the collective, audible gasp from the audience upon seeing the intense green glow emitted from the flask.

Even though I don’t work much with GFP anymore, I still get very excited when I see it.  I suspect that many other people who also work with GFP or any of its color variants BFP (blue), YFP (yellow), RFP (red) etc feel the same way I do about GFP--you just can't wait to see it!

Until next time….

Good Luck and Good Job Hunting!!!!!!!!!!!

 

 

The End of an Era: Ligand Pharmaceuticals to Buy Pharmacopeia for $70 Million in a Stock Deal

New Jersey-based Pharmacopeia, the first-ever combinatorial chemistry company, announced that it had agreed to be purchased by Ligand Pharmaceuticals in a stock deal worth about $70 million. Onetime a leader in combinatorial chemistry and high throughput screening, Pharmacopeia has struggled of late after it jettisoned its profitable molecular modeling division several years ago. While the company was able to advance several of its lead compounds into early phase clinical testing, its  longtime business model, predicated on multiple, small discovery deals with large pharmaceutical companies, was unable to provide enough capital to continue to sustain operations.

Pharmacopeia was established in 1993 after its founders licensed from Columbia University several of the first issued combinatorial chemistry patents. The company was a pioneer in combinatorial chemistry (and subsequently high throughput screening) and was the first to publicly tout the virtues of combinatorial chemistry in drug discovery. By the mid-1990s, many pharmaceutical companies had embraced combinatorial chemistry as the “next big thing” and began eliminating traditional natural product and medicinal chemistry jobs. The industry’s love affair with combinatorial chemistry grew so strong that many companies (most notably Merck), completely eliminated their natural products discovery departments in the late 1990s. Unfortunately, the role of combinatorial chemistry in drug discovery never lived up to its promised potential and was largely abandoned in the early 2000s. Although combinatorial chemistry is now part of the modern day drug discovery paradigm, this onetime “shining star” has largely been relegated to a minor supporting role.

I first became acquainted with Pharmacopeia in 1994 after I took a job with Transcell Technologies, a now-defunct biotechnology company that was co-located with Pharmacopeia in a research facility in Monmouth Junction, NJ. While Transcell and Pharmacopeia shared a cafeteria and some common laboratory equipment, Pharmacopeia employees were strictly forbidden to talk with Transcell employees— lest they inadvertently divulge proprietary combinatorial chemistry concepts that might jeopardize the company’s future. Coincidentally, a guy who lived two doors down from my family and me turned out to be Pharmacopeia’s in-house intellectual property attorney. Although, Ron and I became good friends, he was also extremely tight-lipped about the “goings-on” at Pharmacopeia. Privately-held Pharmacopeia went public in 1995 and at one time, its market capitalization was almost $1.0 billion.

By any reckoning, a 15-year run is outstanding for a biopharmaceutical company. However, as the old adage goes, “All good things must come to an end.” At present, it is not clear, whether or not California-based Ligand will relocate the company or cut jobs. Nevertheless, Pharmacopeia’s impending demise sends a clear signal that the golden age of combinatorial chemistry has ended!

Until next time….

Good Luck and Good Job Hunting!!!