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Effect of serine protease inhibitor, N-alpha-tosyl-L-lysyl-chloromethyl ketone (TLCK), on cell-mediated and cell-free HIV-1 spread.

Abstract
The effect of a serine protease inhibitor, N-alpha-tosyl-L-lysyl-chloromethyl ketone (TLCK), on cell adhesion and resulting cell-to-cell HIV-1 transmission was examined. Cell-mediated viral spread was blocked by 10(-4) M TLCK--the nontoxic dose at which the maximum inhibition of cell adhesion was achieved. TLCK (10(-4)-10(-8) M range) exhibited a similar dose-dependent effect when tested against cell-free virus infection. These findings suggest that TLCK acts by preventing both cell-cell adhesion and viral binding to the target cell. The effect of TLCK could be attributed to an irreversible modification of surface and/or intracellular proteases required for functional activation of HIV-1 envelope glycoproteins.
AuthorsA S Bourinbaiar, R Nagorny
JournalCellular immunology (Cell Immunol) Vol. 155 Issue 1 Pg. 230-6 (Apr 15 1994) ISSN: 0008-8749 [Print] Netherlands
PMID8168146 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Tosyllysine Chloromethyl Ketone
Topics
  • Cell Adhesion (drug effects)
  • Dose-Response Relationship, Drug
  • HIV-1 (growth & development)
  • Humans
  • T-Lymphocytes (microbiology)
  • Tosyllysine Chloromethyl Ketone (pharmacology)
  • Virus Replication (drug effects)

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