{"81781":{"#nid":"81781","#data":{"type":"news","title":"Enzyme Inhibitor: Researchers Test Potential Compounds to Stop Replication of Virus that Causes Adult T-cell Leukemia","body":[{"value":"\u003Cp\u003EThe virus causes the fatal adult T-cell leukemia in up to 10 percent of those infected.\n\u003C\/p\u003E\n\u003Cp\u003ELittle is known about the HTLV-I enzyme, or protease, that cuts long strings of amino acids to form functional proteins that make a mature HTLV-I virus -- a distant cousin of the HIV virus that causes AIDS. About 250 researchers worldwide are studying the HTLV-I protease, and among them are researchers at the Georgia Institute of Technology. They presented their findings April 1st at the 227th national meeting of the American Chemical Society (ACS) in Anaheim, Calif.\n\u003C\/p\u003E\n\u003Cp\u003E\u0022There are currently no good ways to treat HTLV-I and prevent the spread of the virus,\u0022 said Suzanne B. Shuker, an assistant professor of chemistry and biochemistry at Georgia Tech. \u0022Therapies that inhibit the life cycle of the virus have potential as treatments for HTLV-I infection. The protease from HTLV-I is therefore an attractive target for inhibitor design.\u0022\n\u003C\/p\u003E\n\u003Cp\u003EResearchers in Shuker\u0027s laboratory have been studying this protease for five years, building on research begun at Georgia Tech 12 years ago by former Professor Rick Ikeda, now at the National Institutes of Health. As they test possible inhibitor compounds, Shuker and her students are also working to understand more about the enzyme\u0027s activity and structure to help in the development effort. A Georgia Tech and Centers for Disease Control and Prevention (CDC) seed grant is funding the current work.\n\u003C\/p\u003E\n\u003Cp\u003EResearch team member Bryan Herger, a fourth-year Ph.D. student in Shuker\u0027s lab, studies how the protease functions and how it identifies the amino acids it\u0027s supposed to cut. This information helps fourth-year Ph.D. student Kelly Dennison and other team members find compounds that mimic the HTLV-I protease\u0027s process of cutting amino acids. The six compounds they are investigating now contain statine, 4-amino-3-hydroxy-5-phenylpentanoic acid or hydroxyethylamine.  Researchers believe these compounds are potent protease inhibitors.\n\u003C\/p\u003E\n\u003Cp\u003EThey have performed kinetic assays to determine how fast each compound processes the virus proteins. The assays involve a natural substrate consisting of a segment of an amino acid chain that contains a junction where the HTLV-I protease will cut. The substrate is treated with a fluorescent agent that reveals the location of cuts in the amino acid chain. When researchers add a potential inhibitor compound to the substrate, they determine the rate at which it cuts the chain. The slower the rate, the better the inhibitor, Dennison explained.\n\u003C\/p\u003E\n\u003Cp\u003E\u0022Later this year, we will test the most promising of these compounds on actual HTLV-I viruses in CDC labs,\u0022 Dennison added. \n\u003C\/p\u003E\n\u003Cp\u003EMeanwhile, Herger is studying the individual amino acids, or structural elements, which make the HTLV-I protease produce an infectious virus. He is determining which of these elements are involved in binding to the viral proteins and what factors are important in the assembly of viral particles. Once he identifies the approximate arrangement of amino acids, then researchers can develop inhibitors that bind in the same way to those specific amino acids.\n\u003C\/p\u003E\n\u003Cp\u003EHerger uses a lock and key analogy to explain the research. The enzyme is the lock, which has a keyhole.\n\u003C\/p\u003E\n\u003Cp\u003E\u0022We know what the key, or the native viral protein, looks like,\u0022 he said. \u0022And we want to know the shape of the lock to develop other keys to match it and lock it up.\u0022\n\u003C\/p\u003E\n\u003Cp\u003EBased on the amino acids that form the keyhole for the HIV protease, which is very similar to the HTLV-1 protease, researchers can change the HTLV-I protease so it works like HIV.\n\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"Researchers are analyzing several compounds that may inhibit the enzyme that is essential for the reproduction of the Human T-cell Leukemia Virus Type 1 (HTLV-I), which has infected 15 to 20 million people worldwide.","format":"limited_html"}],"field_summary_sentence":"","uid":"27304","created_gmt":"2004-04-04 01:00:00","changed_gmt":"2016-10-08 03:03:38","author":"Matthew Nagel","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2004-04-04T00:00:00-05:00","iso_date":"2004-04-04T00:00:00-05:00","tz":"America\/New_York"},"extras":[],"related_links":[{"url":"http:\/\/gtresearchnews.gatech.edu\/newsrelease\/htlv.htm","title":"Halting Replication"}],"groups":[{"id":"1188","name":"Research Horizons"}],"categories":[{"id":"135","name":"Research"}],"keywords":[],"core_research_areas":[],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cstrong\u003E \u003C\/strong\u003E\u003Cbr \/\u003E\u003Ca href=\u0022http:\/\/www.gatech.edu\/contact\/index.html?id=\u0022\u003EContact  \u003C\/a\u003E","format":"limited_html"}],"email":[],"slides":[],"orientation":[],"userdata":""}}}