Innovation may aid drug development

ON THE TRAIL OF PROTEINS

June 15, 1993|By Douglas Birch and Liz Bowie | Douglas Birch and Liz Bowie,Staff Writers Staff writer Michael Dresser contributed to this story.

A Columbia biotechnology company said yesterday that it has devised a way to make three-dimensional maps of the proteins produced by human cells that control all the basic functions of life -- an advance that could lead to the development of numerous new drugs.

The company, Martek Biosciences Corp., has begun marketing a special food, or growth medium, called "Celtone M," that Martek officials say will permit researchers, for the first time, to draw up detailed blueprints for some of the thousands of very large human proteins whose complex structures have eluded them.

That could help drug researchers find ways to mimic or block the action of those proteins, which include hormones, enzymes and antibodies -- substances that regulate growth and health.

"This is an incredible innovation," said Dr. Joyce Lustbader, a research scientist at the Irving Center for Clinical Research at Columbia University in New York. "This is going to open the solution to many proteins. You can't design a drug rationally unless you know the three-dimensional structure of what you are trying to mimic or block. This is going to open up a whole new industry."

Martek's Dr. Jonathan Miles Brown, who invented Celtone M, said, "Now you have the scenario to describe any protein that can be cloned, basically, if you're clever enough."

Dr. Marius Clore, a protein-mapping specialist with the National Institutes of Health in Bethesda, said Abbott Laboratories, a major pharmaceutical company, announced several months ago that it had developed a similar growth medium for its private research. But Celtone M, he said, probably will be the first product available commercially.

"It's potentially very important," he said. "There are thousands andthousands of proteins whose structures are unknown. . . . You can solve them now."

Henry "Pete" Linsert Jr., Martek's chief executive officer, said yesterdaythat the 8-year-old, privately held company had no idea what the commercial potential of Celtone M might be. "It's primarily a scientific thing right now," he said.

But Dr. Brown said three large U.S. companies are negotiating with Martek for supplies of Celtone M for various research projects.

Dr. Lustbader spent 11 years trying to figure out the structure of a protein called hCG, or human choriogonadotrophin, a hormone vital to human reproduction. Understanding the structure of the hormone could help scientists design new drugs to control fertility.

But Dr. Lustbader found the hormone far too complex to map using the conventional technique, called X-ray crystallography. After seeing a notice in a scientific journal about Celtone M last year, she contacted Dr. Brown and began working with him.

She hasn't solved the structure of HCG yet. But she and Dr. Brown hope to produce enough of a special mixture of Celtone M in the next month or so to make that possible.

Celtone M is basically a soup of 20 amino acids in which all of the carbon and nitrogen atoms are specific, stable isotopes -- carbon 13 and nitrogen 15.

In nature, elements typically occur in several different isotopes. Two isotopes of the same element share the same number of protons in an atom's nucleus but differ in the number of neutrons.

When human and other mammalian cells feed off this purified puree in the laboratory, they produce proteins that contain carbon 13 and nitrogen 15.

Proteins marked in this way can be more easily imaged by Nuclear Magnetic Resonance spectroscopy than proteins with other isotopes or a jumble of isotopes.

NMR spectroscopes bombard atoms with radio frequencies and measure the reaction, or "resonance," of their nuclei. Because different atoms resonate in different ways, the NMR machine can gradually map the location of those atoms and molecules in the proteins.

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