Lipopeptides as Dimerization Inhibitors of HIV-1 Protease

H J Schramm; E D Rosny; M Reboud-Ravaux; J Buettner; A Dick; W Schramm

doi:10.1515/BC.1999.076

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Lipopeptides as Dimerization Inhibitors of HIV-1 Protease

Journal article

Open access

Peer reviewed

Lipopeptides as Dimerization Inhibitors of HIV-1 Protease

H J Schramm, E D Rosny, M Reboud-Ravaux, J Buettner, A Dick and W Schramm

Biological chemistry, v 380(5), pp 593-599

01 May 1999

DOI: https://doi.org/10.1515/BC.1999.076

PMID: 10384967

Featured in Collection : UN Sustainable Development Goals @ Drexel

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Abstract

Human immunodeficiency virus 1

In AIDS therapy, attempts have been made to inhibit the virusencoded enzymes, e.g. HIV-1 protease, using active sitedirected 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 nonnatural amino acids, and an aliphatic Nterminal blocking group. The high inhibitory power of some of the lipopeptides e.g. palmitoylTyrGluLeuOH, palmitoylTyrGlu(Lthyronine) OH, palmitoylTyrGlu(Lbiphenylalanine)OH with low nanomolar Ki valuesin the enzyme test suggests that mimetics with good bioavailability can be derived for AIDS therapy.