October 1, 1999 -- Earlier this week, a team of Howard Hughes Medical Institute (HHMI) investigators reported that it had successfully attacked the human immunodeficiency virus (HIV) in a newly targeted weak spot. Now a second group led by HHMI investigator Peter Kim at the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology has created a new family of chemicals that binds more specifically to the same Achilles' heel, an HIV coat protein known as gp41.

Both groups used three-dimensional images of gp41 to develop molecules that bind to a deep pocket within the gp41 protein, halting its ability to jackknife into a human cell membrane. If HIV loses the function of gp41, it can no longer infect human cells.

In the October 1999 issue of the journal Nature Structural Biology, HHMI investigators Stephen Harrison, Don Wiley and Stuart Schreiber, all of Harvard University, reported that they had generated compounds capable of binding to the susceptible pocket in gp41, as well as other parts of this key HIV protein.

Going one step further, Kim's group succeeded in creating small proteins, or peptides, that bind, as Kim says, "to the gp41 pocket and only to the pocket."

These new findings, described in the October 1, 1999, issue of the journal Cell, demonstrate for the first time that targeting the gp41 pocket alone is sufficient to stop HIV from infecting cells. This is an important discovery because the size and specificity of the compounds developed by Kim's laboratory raise the possibility that patients could take such compounds orally rather than by injection should they prove useful
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
1-Oct-1999