Lipopeptides as dimerization inhibitors of HIV-1 protease

Schramm, H. J.; de Rosny, E.; Reboud-Ravaux, M.; Büttner, J.; Dick, A. and Schramm, W. (1999): Lipopeptides as dimerization inhibitors of HIV-1 protease. In: Biological Chemistry, Vol. 380, No. 5: pp. 593-596

Abstract

In AIDS therapy, attempts have been made to inhibit the virus-encoded enzymes, e.g, HIV-1 protease, using active site-directed inhibitors. This approach is questionable, however, due to virus mutations and the high toxicity of the drugs, An alternative method to inhibit the dimeric HIV protease is the targeting of the interface region of the protease subunits in order to prevent subunit dimerization and enzyme activity, This approach should be less prone to inactivation by mutation, A list of improved 'dimerization inhibitors' of HIV-1 protease is presented. The main structural features are a short `interface' peptide segment, including non-natural amino acids, and an aliphatic N-terminal blocking group. The high inhibitory power of some of the lipopeptides {[}e.g, palmitoyl-Tyr-Glu-Leu-OH, palmitoyl-Tyr-Glu-(L-thyronine)-OH, palmitoyl-Tyr-Glu-(L-biphenyl-alanine)-OH] with low nanomolar K-i values in the enzyme test suggests that mimetics with good bio-availability can be derived for AIDS therapy.

• Item Type: Journal article
• Form of publication: Publisher's Version
• Faculties: Medicine
• Subjects: 500 Science > 540 Chemistry
• ISSN: 1431-6730
• Alliance/National Licence: This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
• Language: English