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Biotech / Medical : progenics -- Ignore unavailable to you. Want to Upgrade?

To: Jim Oravetz who wrote (54)	6/5/2001 10:21:42 AM
From: keokalani'nui	Read Replies (1) \| Respond to of 139

Progenics' Published Study Maps Cellular Attachment Site of HIV; Peptide Decoy Thwarts Viral Docking TARRYTOWN, N.Y., June 5 /PRNewswire/ -- Progenics Pharmaceuticals, Inc. (Nasdaq: PGNX - news) announced the publication of a scientific article describing how researchers designed a novel anti-HIV (human immunodeficiency virus) therapeutic candidate that mimics a cell-surface structure used by the virus to infect cells. This novel compound, known as a sulfated CCR5 peptide, attaches to HIV in a way that specifically inhibits the binding of the virus to human immune system cells. Importantly, sulfated CCR5 peptides target a region on the virus that does not appear to vary across different strains of HIV, suggesting that such molecules might be broadly active against diverse strains of the virus, including those resistant to conventional therapies. In laboratory studies, a sulfated CCR5 peptide that was only nine amino acids long represented the minimum or core structure recognized by HIV in its bid to gain entry into a cell. The findings were reported by a team of scientists from Progenics and the Albert Einstein College of Medicine, Bronx, NY, and are described in the Journal of Virology (Volume 75, issue 12), June 2001. (Logo: newscom.com ) ``A critical step for HIV infection is the binding of a highly conserved region of the virus to a nine amino acid stretch of CCR5,'' said Tatjana Dragic, Ph.D., Assistant Professor of Microbiology and Immunology at Albert Einstein College of Medicine and senior author of the report. ``CCR5 is critical for HIV transmission and replication within the host. HIV is notorious for its genetic diversity and ability to mutate, which provides challenges for conventional antiviral therapies. However, portions of the virus that enable it to perform essential tasks are highly conserved in their molecular structure. The CCR5-binding region of HIV is among the most highly conserved portions of the virus. Therefore, we believe that the CCR5-virus interaction provides a preferred target for therapy.'' In the published report, a series of synthetic CCR5 peptides were tested for potency in binding the surface envelope glycoprotein gp120 derived from diverse HIV isolates. Potent and specific activity was observed for a nine-amino-acid sulfated CCR5 peptide, but not for peptides that were shorter or that lacked sulfate groups. Additional studies examined the binding of mutant gp120 molecules to CCR5. These laboratory studies demonstrated that CCR5 binding is mediated by a highly conserved region of gp120. Progenics' scientists and their collaborators previously identified CCR5 to be a key co-receptor required for wild-type HIV strains to fuse with and infect target cells. Subsequent studies mapped the attachment site for HIV on CCR5 to a short sequence of amino acids that contain sulfate groups, a natural chemical modification. The clinical importance of CCR5 first became apparent in studies of individuals who possess two defective CCR5 genes and were found to be resistant to HIV infection. HIV-infected individuals who possess one defective and one normal CCR5 gene progress to AIDS more slowly than individuals with two normal CCR5 genes. These findings provide in vivo proof-of-concept for CCR5-directed therapy of HIV infection. Progenics is developing its CCR5 monoclonal antibody, PRO 140, as a first-generation CCR5-targeted fusion inhibitor. Progenics is also collaborating with F. Hoffmann-La Roche Ltd to discover and to develop small-molecule drugs that block CCR5 co-receptor function. Peptide, antibody and small-molecule inhibitors of CCR5 co-receptor function belong to a broader category of agents known as HIV entry inhibitors. The Company is conducting preclinical work to optimize its lead sulfated CCR5 peptide in anticipation of human clinical trials.