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2 Scripps Clinic Researchers Are Seen Aiding Product Development

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Times Staff Writer

Two biochemists with key expertise in the field of drug design have accepted positions at the Research Institute of Scripps Clinic, a development that will strengthen the scientific center’s effort to turn its basic research into commercially marketable products.

In addition, the scientists could augment the institution’s continuing work to create and produce man-made enzymes that Scripps researchers hope could revolutionize industrial processes worldwide.

The two researchers, who are to assume positions as full faculty members--the equivalent of full professorships in academia--are:

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Shapes of Proteins

- Jeffrey Skolnick, 35, a professor of chemistry at Washington University in St. Louis and a specialist in protein structure. Skolnick uses computers to determine the specific shapes into which proteins fold themselves to do the work they perform inside a cell.

This structural work is considered essential to finding useful new drugs by designing them rationally, rather than by the conventional method of randomly testing promising chemicals. It also could lead to the design of “better” proteins, such as enzymes that would function outside the normal biological range of temperature and acidity.

- Chi-Huey Wong, 40, a biochemist and professor at Texas A & M University. Wong specializes in using enzymes, the molecules that are the cell’s natural chemistry factory, to make peptides, proteins and carbohydrates necessary for life.

Both are expected to establish labs, complete with postdoctoral researchers and doctoral students they will bring with them, at Scripps in June. A shortage of lab space will require some other researchers to set up labs in rented space at a nearby biotechnology company, Gen-Probe, said William H. Beers, associate director of the research institute.

Eventually, the two might have laboratories in a new Scripps building being planned across North Torrey Pines Road from the institute’s current facilities, Beers said.

Skolnick’s expertise lies in protein structure theory, a field in which he will rely on the massive computing capability available with the Scripps Cray supercomputer, Beers said.

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Root of Malfunctions

Protein structure is key to designing drugs rationally because too little or too much of a particularly shaped protein is often at the root of malfunctions in the body. If a protein’s shape were known, chemists could then design another molecule to lock into that structure as a therapeutic drug.

Skolnick received his doctorate in 1978 from Yale University and has been at Washington University since 1985. Both he and Wong have received the prestigious Alfred P. Sloan Research Fellowship.

Wong joined the Texas A & M faculty in 1983 after completing his doctorate at the Massachusetts Institute of Technology. He became a full professor in 1987. Wong’s awards include selection as a Presidential Young Investigator, a program in which the nation’s most promising young researchers are given no-strings-attached grants of $125,000 to help them get started.

His emphasis on using natural or modified enzymes to create chemicals can be expected to be important to Scripps’ efforts to create rationally designed drugs.

Within the past five years, Scripps has been turning from its past emphasis on basic research in immunology and adding molecular biologists and chemists as part of its effort to produce commercial products. Officials there reiterate their commitment to basic research and immunology, but say it is time to also turn the institute’s years of fruitful basic research into products that will help people.

However, the shift also will mean increasing patent revenues for the institute, as well as increased donations from companies interested in marketing any breakthrough products Scripps produces.

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Catalytic Antibodies

Wong and Skolnick’s expertise also could prove key in a team that has been assembled by Dr. Richard Lerner, director of the Research Institute of Scripps Clinic, to create commercially valuable catalytic antibodies.

The group led by Lerner has published several scientific papers in recent years cataloguing steady progress toward using immunological techniques to design antibodies that will catalyze chemical reactions.

The hope is that these synthetic enzymes can be created to accomplish chemical processes for which no enzymes have ever been available.

Known as abzymes--a hybrid of antibody and enzyme-- these substances would have to be first designed and tested by immunologists and by chemists such as Wong and Skolnick. Then Scripps’ plant molecular biologists would be poised to design a gene that would produce the abzyme and insert it into plants, which eventually could be grown as a crop and harvested for the abzyme.

Although scientists say such a chain of events is complicated and years away, commercial production of abzymes is a tantalizing possibility toward which Lerner has been steadily moving Scripps since taking over as institute director in January, 1987.

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