Lipopeptides as Dimerization Inhibitors of HIV-1 Protease
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H. J. Schramm
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 Ki valuesin the enzyme test suggests that mimetics with good bio-availability can be derived for AIDS therapy.
Copyright ©1999 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- Biosynthesis of Glycosylphosphatidylinositols in Mammals and Unicellular Microbes
- Activation of DNA Replication in Yeast by Recruitment of the RNA Polymerase II Transcription Complex
- On the Role of Symmetrical and Asymmetrical Chaperonin Complexes in Assisted Protein Folding
- Regulation of Cathepsin B Activity by Cysteine and Related Thiols
- Epitope Mapping of the Monoclonal Antibody MM12.10 to External MDR1 P-Glycoprotein Domain by Synthetic Peptide Scanning and Phage Display Technologies
- Molecular Mimicry between a Monoclonal Antibody and One Subunit of Crotoxin, a Heterodimeric Phospholipase A2 Neurotoxin
- Enzyme-Linked Immunosorbent Assay for the Measurement of JNK Activity in Cell Extracts
- Mitochondrial DNA Acts as Potential Promoter of the Baculovirus RNA Polymerase
- In Vitro Phosphorylation of Purified Glycosylphos-phatidylinositol-Specific Phospholipase D
- Cathepsin S and Cruzipain Are Inhibited by Equistatin from Actinia equina
- Lipopeptides as Dimerization Inhibitors of HIV-1 Protease
