Correlation Engine 2.0
Clear Search sequence regions


  • acid (2)
  • activity (2)
  • drug targets (1)
  • effects treatment (1)
  • hiv (1)
  • humans (1)
  • hydrogen (1)
  • hydroxyl (2)
  • proteases (7)
  • transport (1)
  • Sizes of these terms reflect their relevance to your search.

    Aspartic proteases (APs) are a class of enzymes engaged in the proteolytic digestion of peptide substrates. APs play important roles in physiological and infectious pathways, making them plausible drug targets. For instance in the treatment of HIV infections, access to an efficient combination of protease and reverse transcriptase inhibitors have changed a terminal illness to a chronic but manageable disease. However, the benefits have been limited due to the emergence of drug resistant viral strains, poor pharmacokinetic properties of peptidomimetic inhibitors and adverse effects associated with the treatment. In the 1980s, D. Rich and co-workers proposed a novel strategy for the development of AP inhibitors by replacing the secondary hydroxyl group with a tertiary alcohol as part of the transition state (TS) mimicking moiety. This strategy has been extensively explored over the last decade with a common belief that masking of the polar group, e.g. by intramolecular hydrogen bonding, has the potential to enhance transcellular transport. This is the first review presenting the advances of AP inhibitors comprising a tertiary hydroxyl group. The inhibitors have been classified into different tert-hydroxy TS mimics and their design strategies, synthesis, biological activities, structure-activity-relationships and X-ray structures are discussed. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

    Citation

    Hitesh V Motwani, Maria De Rosa, Luke R Odell, Anders Hallberg, Mats Larhed. Aspartic protease inhibitors containing tertiary alcohol transition-state mimics. European journal of medicinal chemistry. 2015 Jan 27;90:462-90

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 25481814

    View Full Text