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UA chemists score in war against HIV

Matt Heistand Arizona Daily Wildcat Dr. Jacquelyn Gervay (front left), a UA researcher, is working on a new way to combat HIV. Gervay is with lab students senior Xenia Frisby, junior Malen Link, third-year graduate student Son Lam, post doctorate student Abhijit Bhat, senior Mark Smith and post doctorate student Michael Hadd.

The race to find a cure for HIV is getting a major boost from a team of UA researchers.

A University of Arizona chemist and her colleagues are working to stop the virus before it is contracted, rather than treating it upon infection.

"The drugs currently on the market for HIV are designed to work once it (the virus) has entered a cell," said Jacquelyn Gervay, an associate professor in UA's Department of Chemistry. "Our approach is to stop the virus from getting in the cell in the first place."

Gervay, the lead investigator for the HIV research project, specializes in carbohydrate chemistry - a field that explores the use of carbohydrates as potential drug candidates.

"In the last 10 years, it's been recognized that carbohydrates serve different roles," Gervay said. "We've been dealing with carbohydrates in terms of their ability to recognize other cells."

Her contributions to this area of research recently netted her the prestigious Horace Isbell Prize at this year's Wolfrom and Isbell Awards Symposium held Aug. 22-26 in New Orleans, La.

The development of new anti-HIV medications currently involves the mass production of drugs that are then screened to identify those with potential. While this process has yielded some positive results, it is both costly and time-consuming.

The innovative approach devised by Gervay and her colleagues will allow them to create 'smart' drugs that specifically target the HIV virus.

"We're very excited about the results to date," said David O'Brien, an associate professor in the UA department of chemistry, who has worked with Gervay on the current HIV research project. "This is really just the start of an extensive series of studies."

HIV typically infects two main types of cells - immune cells and those cells associated with the sexual transmission of the virus. The work of Gervay and her colleagues focuses on those cells involved with sexual transmission.

The HIV virus is coated with carbohydrate-protein complexes called gp120. Human cells have specific binding sites that recognize gp120 and allow the virus to enter the cell.

"It was known that HIV recognizes a carbohydrate in these cells," Gervay said. "We look for a process that involves carbohydrates, and then make carbohydrates that mimic that process."

Gervay and her fellow researchers realized that if they could create a drug to mimic the natural binding sites for gp120, they could conceivably prevent HIV from entering human cells.

The first mimic was designed by Kathie McReynolds, one of Gervay's former students. Graduate student Denise Scofield is credited with having developed the second mimic.

The researchers then used their expertise in synthetic chemistry to create non-natural compounds that could mask gp120 without posing a threat to healthy cells.

The next challenge for Gervay and her colleagues is to find a way to successfully attach these synthetic coatings to gp120. Unfortunately, the researchers have had difficulties in locating one area where these compounds will strongly attach to gp120.

To address this problem, Gervay's team is attaching different types of mimics to three different areas on gp120. Their belief is that several weak attachments will work better than a single strong attachment.

This research effort is being funded by the National Institutes of Health and the National Science Foundation with additional help from the Sloan Foundation and Eli Lilly.

Gervay said that much work remains to be done in this area and that it will be at least three to six years before any new HIV drug hits the market.

"It's my students that do the work," Gervay said. "What's rewarding for me is seeing my students grow and prosper from the whole process."