HIV protease-mediated activation of sterically capped proteasome inhibitors and substrates

Dennis L. Buckley, Timothy W. Corson, Nicholas Aberle, Craig M. Crews

Research output: Contribution to journalArticle

9 Scopus citations


Strategies for selectively killing HIV-infected cells present an appealing alternative to traditional antiretroviral drugs. We show here the first example of an inactive "Trojan horse" molecule that releases a cytotoxic, smallmolecule proteasome inhibitor upon cleavage by HIV-1 protease. As a proof-of-concept strategy, the protein avidin was used to block entry of the compound into the proteasome in the absence of HIV-1 protease. We demonstrate that this strategy is also feasible without requiring an exogenous protein; a polylysine dendrimer-containing molecule is unable to enter the proteasome until cleaved by HIV-1 protease. These results demonstrate that conditional proteasome inhibitors could prove useful in the development of new tools for chemical biology and future therapeutics.

Original languageEnglish (US)
Pages (from-to)698-700
Number of pages3
JournalJournal of the American Chemical Society
Issue number4
StatePublished - Feb 2 2011

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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