Development of Anti-HIV Agents Based on Chemical Biology

• Tamamura Hirokazu

  Department of Medicinal Chemistry, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University

Bibliographic Information

Other Title

• ケミカルバイオロジーを基盤とした抗HIV剤の創製
• ケミカルバイオロジー オ キバン ト シタ コウHIVザイ ノ ソウセイ

Abstract

  Recently, highly active anti-retroviral therapy (HAART), which involves a combinational use of reverse transcriptase inhibitors and HIV protease inhibitors, has brought us a great success in the clinical treatment of AIDS patients. However, HAART has several serious clinical problems. These drawbacks encouraged us to find novel drugs and increase repertoires of anti-HIV agents with various action mechanisms. The recent disclosing of the dynamic supramolecular mechanism in HIV-entry has provided potentials to find a new type of drugs. To date, we have synthesized HIV-entry inhibitors, especially coreceptor CXCR4 antagonists. In addition, CD4 mimics in consideration of synergic effects with other entry inhibitors or neutralizing antibodies have been developed. The development of the above anti-HIV agents is based on the concept of reverse chemical genomics, in which target molecules are fixed. On the other hand, based on the concept of forward chemical genomics, in which active compounds are searched according to the screening of random libraries, effective peptide leads such as integrase inhibitors derived from fragment peptides of HIV-1 Vpr have been discovered. As such, from a point of view on chemical biology, anti-HIV leads have been found utilizing reverse and forward chemical genomics. Furthermore, antibody-based therapy or AIDS vaccine is still thought to be a promising treatment. Thus, peptidic antigen molecules based on artificial remodeling of the dynamic structures of a surface protein gp41 in HIV fusion have been developed. The present chemical biology approaches would be essential for discovery of anti-HIV agents in consideration of cocktail therapy of AIDS.<br>

Journal

• YAKUGAKU ZASSHI

  YAKUGAKU ZASSHI 132 (1), 69-78, 2012-01-01

  The Pharmaceutical Society of Japan

Keywords

• anti-human immunodeficiency virus (HIV) agent
• AIDS vaccine
• chemical biology
• CXCR4 antagonist
• CD4 mimic
• integrase inhibitor

Details

• CRID: 1390282681104607232
• NII Article ID: 130001871964
• NII Book ID: AN00284903
• DOI: 10.1248/yakushi.132.69
• ISSN: 13475231
• ISSN: 00316903
• NDL BIB ID: 023456578
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I023456578
• Web Site: https://www.jstage.jst.go.jp/article/yakushi/132/1/132_1_69/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2012143224
• Text Lang: ja
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed