Imagine ordering a part to repair your car, and having the new part delivered in pieces you must first assemble.

A similar situation often occurs in treating cancer, because the components needed to put the brakes on the cells' abnormal growth can be readily delivered through the cell membrane only in pieces that then must be assembled by the cell.

Scientists at Purdue University have developed a method for getting these compounds, called nucleotides, into tumor cells -- already assembled.

The method may lead to the development of new, more powerful treatments that have fewer side effects and are less likely to produce drug resistance in patients being treated for cancer and certain viruses such as HIV, says Richard Borch, principal investigator of the study who is the Lilly Distinguished Professor of Medicinal Chemistry and Molecular Pharmacology at Purdue.

"Potentially this system will work for all types of cancer, and it may prove useful in treating cancers that have been resistant to other treatments, such as pancreatic cancer," Borch says.

Nucleotides, which act as building blocks for the molecules that make up DNA and RNA, also carry out several essential functions needed for cell replication. By delivering specific forms of nucleotides to a cell, scientists can throw a chemical wrench into the cell's machinery to block the replication of viruses and cancer cells.

"Nucleotides can be used in a number of ways to inhibit a specific critical pathway that a cell requires to proliferate," Borch says. "The problem was, we couldn't deliver nucleotides directly into a cell because they carry a negative charge that prevents them from crossing the cell's membrane."

Many current therapies instead deliver precursor compounds that the cell then uses to "build" nucleotides.

Borch and his group have developed a way to hide the negative charge, creating a "stealth compound" with specially designed nucleotides that c
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Contact: Susan Gaidos
sgaidos@uns.purdue.edu
765-494-2081
Purdue University
30-Apr-2000