Inhibition of HIV-1 replication by a Tat RNA-binding domain peptide analog

J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Feb 1;17(2):104-11. doi: 10.1097/00042560-199802010-00002.


The peptidic compound, N-acetyl-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-Cys(biotin)-NH2 (Tat10-biotin), contains the 9-amino acid sequence from the basic domain of the Tat protein responsible for specific interaction with TAR RNA. The cysteine residue provides an attachment site for biotin, which acts as a cellular uptake enhancer. Tat10-biotin binds a fragment of TAR RNA (deltaTAR) avidly and specifically, as measured in an electrophoretic gel shift assay. Tat10-biotin inhibited tat gene-induced expression of a stably transfected chloramphenicol acetyl transferase (CAT) reporter gene linked to the HIV-1 long terminal repeat (LTR) in a model cell assay, but did not inhibit phorbol ester-induced expression of CAT, thereby demonstrating a Tat-dependent mechanism of inhibition. Inhibition of HIV-1 replication after acute infection of MT2 cells was demonstrated by absence of HIV-induced syncytium formation and cytotoxicity, as well as by suppression of reverse transcriptase production. These results suggest that a peptide or peptide mimetic capable of competing with the TAR RNA-binding domain of Tat protein might be useful as a therapeutic agent for AIDS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Biological Transport
  • Biotin / analogs & derivatives*
  • Biotin / pharmacology
  • Chloramphenicol O-Acetyltransferase / biosynthesis
  • HIV Long Terminal Repeat
  • HIV-1 / drug effects*
  • HIV-1 / growth & development
  • Oligopeptides / pharmacology*
  • Peptide Fragments / pharmacology
  • Protein Binding
  • RNA, Viral / drug effects*
  • RNA-Binding Proteins / pharmacology*
  • Recombinant Fusion Proteins / biosynthesis
  • Transcriptional Activation / drug effects
  • Virus Replication / drug effects


  • Anti-HIV Agents
  • Oligopeptides
  • Peptide Fragments
  • RNA, Viral
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • Tat10-biotin
  • Biotin
  • Chloramphenicol O-Acetyltransferase