FEATURE STORY — May/June 2009

 

On a Molecular Mission

As a UIC student, Rina Dukor was given a research problem by chemistry professor Timothy Keiderling that would take her four years to solve and yield a scientific breakthrough. Today, she co-owns BioTools Inc. and helps the pharmaceutical industry solve its toughest problems

By Lisa Sedelnik
Photography by Donna Victor

Rina Dukor’s vision and drive resulted in the first off-the-shelf vibrational circular dichroism spectrometer. The instrument helps pharmaceutical companies such as Eli Lilly and GlaxoSmith Kline meet FDA testing regulations for chiral-based drugs.

At age 15, just two weeks after emigrating to the United States with her family from what was then the Soviet Union, Rina Dukor ’86 LAS, MS ’87 LAS, PHD ’91 LAS, had already managed to land two part-time jobs selling Avon and Amway products door-to-door. “When I came to America I immediately started working as an entrepreneur,” says Dukor.

Even though she displayed a knack for entrepreneurship and came from a family of innovators (her uncle Alexander, an inventor, started a company when he emigrated to the United States), Dukor never imagined she would eventually become her own boss.

“I didn’t leave graduate school at UIC thinking I was going to become an entrepreneur, absolutely not,” admits the 43-year-old Dukor. “I thought I would [enter the field of science] but not [with] my own company.”

Today, despite her earlier reservations, she  does both successfully. Dukor is president and CEO of BioTools Inc., a Jupiter, Fla.-based firm that she co-founded in 2001 with Professor Laurence Nafie of Syracuse University. BioTools provides instrumentation and services to pharmaceutical and biotechnology firms in several niche markets. The company has commercialized three products for the life sciences industry, thanks to Dukor’s vision and drive.

The Detour to America
Dukor may never have pursued a career in science had it not been for one of life’s unexpected turns. Born to a Jewish family and raised in Moscow during the Soviet Union era, Dukor as a young girl enjoyed reading travel books, taking English classes and listening to American music. She also dreamed of becoming a translator for government officials, in part, because she believed it would be her ticket to the outside world.

“When I was growing up in Russia [during the 1970s], it was very hard to travel,” recalls Dukor. “So if I became a translator for a politician ... I [would be able to] travel with that individual and see the world.”

Although Dukor was an applied student, her mother feared she wouldn’t have an opportunity to attend a university because of her religious affiliation. With an uncle already living in Chicago, the family decided to emigrate to the United States in 1980 to reconnect with other family members and have a chance at a better life. They moved to Chicago’s Rogers Park neighborhood where Dukor, then 15, attended Roger C. Sullivan High School.

Upon graduation, Dukor set her sights on attending Northwestern University. But after reviewing Northwestern’s tuition and fees, she decided to consider UIC. To test the waters, Dukor sat in on a chemistry class with Eric Gislason, then-UIC professor and vice chancellor of research, and was extremely impressed. “I thought he was the best teacher I had ever seen,” she recalls.

The UIC Experience
Now pursuing a double major in chemistry and biology, Dukor was advised by friends to take a research class during her third year of undergraduate studies. After class one day, she approached Timothy Keiderling, UIC professor of chemistry, and asked him what type of research he did. “We sat down and talked, and I did not understand a single word, except for one, and that was ‘protein,’” she recalls.

Once in the lab, Dukor proved to be a team player who enjoyed solving tough questions. “She would bring enthusiasm, insight and energy to a project,” says Keiderling. “She is [the kind of] person who has the ability and the energy to finish things, and it’s incredibly important [in science] to do that.”

Yet the research question related to proteins that Keiderling posed to Dukor could not be solved overnight. In fact, it was so complex that Dukor could not find a solution by quarter’s end. Keiderling gave her an incomplete grade and instructed her to return in the summer to finish the project.

But Dukor couldn’t afford to do that. “It was just my mom, brother and me and I had to chip in,” she explains. “I had some financial aid and a scholarship for women in science and mathematics, but I had to work to [help] pay for [our] apartment and for everything else.”

Dukor returned to her research in the fall quarter. She also began applying to various graduate schools, but eventually decided to remain at UIC for both her advanced degrees. “I was so intrigued by the problem, and Keiderling was so interesting to work with, I just didn’t want to give that up,” she admits.

The research Dukor had embarked upon during her junior year would eventually occupy her for the next four years. What she helped discover was that the major structural component in proteins, known as the random coil, was not random at all. Instead, it had a specific helical structure called polyproline II. The identification of this molecular structure represented a major scientific breakthrough and, as a result, is often cited in scientific journals.

“Knowing the protein structure is critical for drug design and the use of proteins in all aspects of life,” explains Dukor. “If we do not know or do not understand parts of overall structure, or if we do not understand how proteins fold, we cannot design drugs. Our research at UIC uncovered this structural component and solved the debate in the literature and opened doors to many other studies.”

Dukor’s studies with Keiderling also exposed her to a form of spectroscopy known as vibrational circular dichroism or VCD—a technology that would later play a major role in her success as an entrepreneur. 

Corporate Life and Entrepreneurship
In 1991, Dukor joined Amoco Technology’s Biotechnology Division as a postdoctoral research associate.

At the Biotechnology Division, Dukor was tasked with establishing a laboratory to perform vibrational spectroscopy of proteins and nucleic acids. She also developed a simpler technique, which uses infrared light to examine protein structures. But the piece of equipment Dukor wanted most for her lab, an “off-the-shelf” VCD spectrometer, was unobtainable. “I became frustrated because I knew that VCD was a powerful technique but no one dared to commercialize it,” she explains. “And Amoco was not in the business of building instruments, so I could not build one there.” Nevertheless, Dukor received permission from Amoco’s management to pursue the development of a VCD spectrometer on her own time.

A VCD spectrometer, for example, can be used to determine the absolute configuration of chiral compounds. All biological molecules of significance—including sugars, nucleic acids and proteins—are chiral. Chiral molecules also are found in prescription drugs such as Lipitor. These molecules have two non-superimposable, mirror-image forms (think of how a pair of hands—left and right—mirror each other), and are referred to as left or right enantiomers or stereoisomers. VCD spectrometers measure the natural optical activity of a chiral molecule by determining its differential response to left and right circularly polarized radiation.

As it happens, several developments in the pharmaceutical industry would push verification of chiral molecules and VCD technology to the forefront, making Dukor’s “home” research project a sound one. Key among them was a new policy statement issued in May 1992 by the U.S. Food and Drug Administration that specified the testing requirements for new drugs containing chiral molecules. In particular, the regulations called for pharmaceutical companies to prove the absolute configuration of a drug’s chiral molecule—critical because one of the two enantiomers could have potentially dangerous side effects. In addition, new asymmetric and chiral separation technologies were making it more economical to develop and market new stereoisomer drugs.

The combination of these factors motivated Dukor to meet with Nafie and begin discussions on bringing a VCD spectrometer to market. “Rina has the business sense, the business drive and knowledge of people,” says Nafie, reflecting on their business partnership. “What I bring to the table is an understanding of the theory and the science [behind] the instrumentation.”

The two flew to Quebec, Canada, to meet with ABB Bomem, a manufacturer of spectrometers and other instrumentation, and negotiate a business deal where the company would fund the development of ChiralIR, BioTool’s first VCD spectrometer, in return for a percentage of the profits.

In December 2000, Dukor left Amoco (now known as Vysis) to devote herself full-time to formally launching BioTools. “In my heart, I knew I [had] to quit, but it was hard to do because of family reasons,” she says. “I had a great salary, great benefits and a good job.” Had she not resigned at that time, Vysis would have forced her to surrender all of her intellectual property rights related to BioTools, notes Nafie.

Despite those reservations, Dukor’s decision has turned out to be the right one, given today’s pharmaceutical market. Seventy percent of the new small-molecule drugs approved by the FDA in 2007 contained at least one chiral center, according to Chemical & Engineering News magazine. In addition, Pharmaceutical Tech­nology reported that single-enantiomer therapeutics accounted for 37 percent of the total formulation pharmaceutical market in 2005, and single-enantiomer products over the past five years have had a compound growth rate of 11 percent. Most of the market’s new blockbuster drugs (those projected to produce more than $1 billion annually in sales) are chiral-based. Keiderling credits Dukor with recognizing the value that VCD would have in the pharmaceutical industry.

At home in the “Sunshine State”
To help meet the needs of this growing pharmaceutical market, BioTools now offers the ChiralRAMAN and PROTA/ BioIR, as well as an array of services, such as feasibility studies and laboratory analysis.

BioTools’ flagship product, the ChiralIR, uses VCD to determine the structure of chiral molecules and the conformations of chiral biological molecules, such as amino acids, peptides, proteins, sugars and DNA. “It’s a very powerful instrument” that helps pharmaceutical and life sciences companies such as GlaxoSmith Kline and Eli Lilly determine a molecule’s absolute configuration, says Dukor.

VCD technology also saves pharmaceutical companies time and money. “If a drug has chirality issues, the FDA requires that both [the left and right] enantiomers be thoroughly tested,” says Dukor. Previously, determining a drug’s chiral structure required growing a crystal of the enantiomer and performing X-ray crystallography. “It often takes months to grow a crystal, and it requires a minor modification to the molecule,” she explains. By comparison, “VCD allows chemists to determine the chirality structure ... with no need to grow a crystal. It’s inexpensive and fast—days and weeks compared to months,” says Dukor.

The PROTA product, also based on knowledge Dukor gained while working in Keiderling’s lab, relies on infrared absorption spectroscopy, computer algorithms (one of which originated from UIC) and databases. It’s currently used by more than 60 of the leading biopharmaceutical companies worldwide (including Amgen, Pfizer, Protein Design Labs Inc. and Wyeth), and allows scientists to analyze the structure of proteins as well as the formulation and stability of protein pharmaceutical products.

The ChiralRAMAN, which BioTools introduced in 2003, measures Raman optical activity to make a “fingerprint” (via polarized light) of a molecule’s absorption pattern or spectrum. Today, the product is used primarily in academic settings to study the conformations and shapes of folds of bio-molecules such as proteins, peptides, RNA, DNA and viruses.

In 2005, after chairing a conference in Fort Lauderdale, Fla., and reading a local newspaper headline that said: “Governor [Jeb] Bush Lands Scripps” (Scripps Florida is a state-of-the-art biomedical research institute), Dukor decided to relocate BioTools from Wauconda to Jupiter. “I really wanted the company to be in a growing [life sciences] cluster,” she says. “So after looking at the pluses and minuses, I made the move.”

Dukor has never looked back. The relocation has proved beneficial to both her family (son Alan is 15 and daughter Anna is 11) and the company, which has since grown from two employees to 10. “In Chicago, there was little, if any, collaborative effort with the company next door,” explains Dukor. “But here, everybody pulls together to grow this life sciences cluster. You can actually be a good collaborator and share facilities ... In Ill­inois, I wasn’t able to do that.”

Dukor does have some regrets from her entrepreneurial activities. She is still reeling from bad credit due to the money (including credit cards and Amoco stock options) she has funneled into BioTools over the years. Fortunately, the company now has an angel investor, thanks to the publicity it received since relocating to Florida.

“If I were to do this all over again, I probably would have gone out and raised some capital,” Dukor admits. “However, I’ve never lost control of the company. It’s taken a huge toll on me personally, but it’s been worth it. If I can help one person, one other scientist, I am thrilled.”