Subject: Scientists Unveil Structure of Protein Targeted by AIDS 
Date: Published: 11/29/90 (69 lines)
Source: Wall Street Journal. Copyright Dow Jones & Co. Inc.

    Technology & Medicine:
    Scientists Unveil
    Structure of Protein
    Targeted by AIDS
    ----
    By Marilyn Chase
    Staff Reporter of The Wall Street Journal

    Two independent teams of scientists unveiled the atomic
 structure of the human protein targeted by the AIDS virus
 when it infects the body.
    Their painstaking reconstruction of the protein's
 three-dimensional design may yield insights into how the
 virus invades human cells.  This, in turn, could lead to
 improved treatments for acquired immune deficiency syndrome.
    Teams led by Wayne Hendrickson of Columbia University and
 Stephen Harrison of Harvard published their findings in the
 current issue of the British journal Nature.  Their work was
 done under sponsorship of the Howard Hughes Medical
 Institute.
    The reports -- culminating three years of work -- disclose
 the precise crystalline structure of the protein known as CD4
 on the surface of specialized white blood cells called T4
 cells.  Although these cells normally act as immune sentries,
 they are invaded by the virus as it homes in on CD4.  The
 virus then commandeers the cell's reproductive machinery to
 make more viruses.
    More than half a dozen companies now are developing drugs
 that use synthetic copies of the CD4 protein as decoys to
 block the AIDS virus in the body.  So far, however, such
 therapies haven't proven effective against the disease in
 human clinical trials.
    Mr. Hendrickson, professor of biochemistry and biophysics
 at Columbia, said, "There's no doubt (CD4's crystal
 structure) suggests alternative chemical structures" for such
 therapies.  "Whether they bind with high enough affinity to
 block (infection) remains to be seen," he said.
    Outside scientists working with CD4 agreed the reports by
 the Hendrickson and Harrison teams were a necessary step that
 might help them refine AIDS drugs and, in time, make them
 more useful.
    "It's very elegant work," said Jerome E. Groopman, a
 researcher at New England Deaconess Hospital in Boston.  "It
 should help us understand better how the virus interacts with
 CD4, and why the virus might have eluded current CD4-based
 therapies."
    "It's very important ...It provides one half of the
 puzzle," said Daniel Capon, who pioneered CD4 work at
 Genentech Inc. before leaving to join Cell Genesys Inc. of
 Foster City, Calif.  What remains is for scientists to find
 the crystal structure of the part of the AIDS virus that
 binds to CD4.  When that is done, Mr. Capon said, "It should
 be a great boon to drug designers."
    However, he cautioned that X-ray crystallography is a
 scientific "crapshoot," involving both skill and luck in
 obtaining crystals of key substances.  "We're very fortunate
 that this work on CD4 has been accomplished as quickly as it
 was," Mr. Capon said.  Finding the crystal structure of the
 corresponding part of the virus, he cautioned, "may be some
 years off."

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