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Substrate Cleavage by HIV-1 Proteinase

  • R. A. Jupp
  • A. D. Richards
  • L. H. Phylip
  • J. Kay
  • J. Konvalinka
  • P. Strop
  • V. Kostka
  • P. E. Scarborough
  • W. G. Farmerie
  • B. M. Dunn
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 306)

Abstract

The pol open reading frame (ORF) of the human immunodeficiency virus (HIV-1) encodes three distinct enzymes, one of which is an aspartic proteinase (PR). Point mutations introduced at the active site of this enzyme result in an inability to form infectious virions1 thus emphasizing the paramount importance of PR in viral maturation. Proteinase has thus become a strategic target for the development of compounds that might have therapeutic value in the treatment of AIDS.2 By preference, such compounds should be specific for the target, HIV-PR and should not have side effects by interacting with similar enzymes present in the human body, such as have been observed for example with anti-viral agents (e.g. AZT that act against reverse transcriptase RT). The design of specific PR inhibitors is facilitated considerably by a detailed understanding of the molecular topography of the PR active site. To this end, several series of synthetic chromogenic substrates have been used to unravel the subsite preferences of this important enzyme. In some cases, the requirement for certain residues to be present in particular locations in native protein substrates in order to ensure effective hydrolysis by PR has also been examined.

Keywords

Aspartic Proteinase Isoleucine Residue Effective Hydrolysis Synthetic Chromogenic Substrate Scissile Peptide Bond 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • R. A. Jupp
    • 1
  • A. D. Richards
    • 1
  • L. H. Phylip
    • 1
  • J. Kay
    • 1
  • J. Konvalinka
    • 2
  • P. Strop
    • 2
  • V. Kostka
    • 2
  • P. E. Scarborough
    • 3
  • W. G. Farmerie
    • 3
  • B. M. Dunn
    • 3
  1. 1.Department of BiochemistryUniversity of Wales College ofCardiffCardiffUK
  2. 2.Institute of Organic Chemistry & BiochemistryCzechoslovak Academy of SciencePrague 6CSFR
  3. 3.Department of Biochemistry and Molecular BiologyUniversity of FloridaGainesvilleUSA

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