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

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

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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
Pages (from-to)698-700
Number of pages3
JournalJournal of the American Chemical Society
Volume133
Issue number4
DOIs
StatePublished - Feb 2 2011

Fingerprint

HIV Protease
Proteasome Inhibitors
Chemical activation
Proteasome Endopeptidase Complex
Substrates
Dendrimers
Molecules
Polylysine
Avidin
Proteins
HIV
Pharmaceutical Preparations
Human immunodeficiency virus 1 p16 protease
Peptide Hydrolases
Therapeutics

ASJC Scopus subject areas

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

Cite this

HIV protease-mediated activation of sterically capped proteasome inhibitors and substrates. / Buckley, Dennis L.; Corson, Timothy; Aberle, Nicholas; Crews, Craig M.

In: Journal of the American Chemical Society, Vol. 133, No. 4, 02.02.2011, p. 698-700.

Research output: Contribution to journalArticle

Buckley, Dennis L. ; Corson, Timothy ; Aberle, Nicholas ; Crews, Craig M. / HIV protease-mediated activation of sterically capped proteasome inhibitors and substrates. In: Journal of the American Chemical Society. 2011 ; Vol. 133, No. 4. pp. 698-700.
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