NEW ORLEANS, La.-- Chemists at the University of Arizona in Tucson may be
closer than ever to stopping HIV (human immunodeficiency virus). They are
using a unique approach based on understanding the interactions of the virus
with cells at the most fundamental, molecular level.
Jacquelyn Gervay, UA associate professor of chemistry, and her colleagues
have conducted several studies of these interactions and are presenting
their results at the American Chemical Society (ACS) national meeting in New
Orleans, Aug. 22 _ 26.
Gervay gave an overview of the new approach at the Wolfrom and Isbell Awards
Symposium at 2 p.m. yesterday (Aug. 22 ) in the Ernest Morial Convention
Center. Gervay is this year_s recipient of the Horace Isbell Prize.
"We started with the disease process, trying to really understand it, and
then asking ourselves what we, as chemists, could do," Gervay said.
This is an unusual approach in the area of drug development. Pharmaceutical
companies operate under severe time constraints. So they they use new
technologies to produce many different drugs and then screen out those few
that have potential. Full understanding of how the drug works often comes
much later, if at all.
Gervay's approach is just the opposite. It has enabled her research group to
design a drug that will specifically target the HIV virus.
Medications currently available to treat those infected with HIV have one
thing in common: They are designed to interrupt the reproduction of the
virus after it has entered its human target cell. Gervay's plan is to
prevent the virus from entering the cell. She and postdoctoral fellow Mike
Hadd formulated this approach after learning how viruses recognize their
The HIV virus is covered with carbohydrate-protein complexes called gp120.
Gp120 recognizes a specific binding site on immune cells, where it attaches
and invades the cells. The researchers realized that if they could design a
drug to "coat" gp120, then the HIV virus wouldn't be able to attach to the
immune cells. This raised the question of what coating to use _ a question
that has been the group_s major challenge.
The first problem was interference with the body's normal, natural immune
response. If the virus were coated with a naturally recognized substance,
the HIV virus might still be able to slip past the cell_s defenses. The
coating might also be toxic.
Therefore, the coating had to be a substance that does not occur naturally.
Gervay's group used its expertise in synthetic chemistry to make compounds
that mimic the natural binding sites for gp120. These mimics are designed to
be similar enough to bind to the virus, yet different enough to escape
recognition by healthy cells _ or to be only weakly recognized.
The second problem was attaching the coating. Finding one place where the
coating would strongly attach to gp120 is difficult. Gervay's group has
devised a creative solution: They are attaching different mimics to three
different places on gp120. The idea is that several weaker attachments will
be collectively more effective than a single, strong attachment.
Furthermore, the mimics will be positioned so they bind quickly and
irreversibly to gp120, and only to gp120.
At the ACS meeting, Gervay talked about research conducted by former student
Kathie McReynolds, who designed the first mimic and studied its attachment
to gp120. Graduate student Travis Gregar will present his research on the
design of a second mimic on Wednesday at 3 p.m. in room 145 of the
S. Scott Saavedra and David O_Brien, also of the UA chemistry faculty, also
worked on the project with Gervay_s group. The research is funded by the
National Institutes of Health and the National Science Foundation. The Sloan
Foundation and Eli Lilly also have provided support.