Jump to main content
Jump to site search

Issue 45, 2015
Previous Article Next Article

Attenuating HIV Tat/TAR-mediated protein expression by exploring the side chain length of positively charged residues

Author affiliations

Abstract

RNA is a drug target involved in diverse cellular functions and viral processes. Molecules that inhibit the HIV TAR RNA–Tat protein interaction may attenuate Tat/TAR-dependent protein expression and potentially serve as anti-HIV therapeutics. By incorporating positively charged residues with mixed side chain lengths, we designed peptides that bind TAR RNA with enhanced intracellular activity. Tat-derived peptides that were individually substituted with positively charged residues with varying side chain lengths were evaluated for TAR RNA binding. Positively charged residues with different side chain lengths were incorporated at each Arg and Lys position in the Tat-derived peptide to enhance TAR RNA binding. The resulting peptides showed enhanced TAR RNA binding affinity, cellular uptake, nuclear localization, proteolytic resistance, and inhibition of intracellular Tat/TAR-dependent protein expression compared to the parent Tat-derived peptide with no cytotoxicity. Apparently, the enhanced inhibition of protein expression by these peptides was not determined by RNA binding affinity, but by proteolytic resistance. Despite the high TAR binding affinity, a higher binding specificity would be necessary for practical purposes. Importantly, altering the positively charged residue side chain length should be a viable strategy to generate potentially useful RNA-targeting bioactive molecules.

Graphical abstract: Attenuating HIV Tat/TAR-mediated protein expression by exploring the side chain length of positively charged residues

Back to tab navigation

Supplementary files

Publication details

The article was received on 17 Aug 2015, accepted on 15 Sep 2015 and first published on 24 Sep 2015


Article type: Paper
DOI: 10.1039/C5OB01729G
Citation: Org. Biomol. Chem., 2015,13, 11096-11104
  •   Request permissions

    Attenuating HIV Tat/TAR-mediated protein expression by exploring the side chain length of positively charged residues

    C. Wu, Y. Chen, S. Liu, F. Chien, C. Mou and R. P. Cheng, Org. Biomol. Chem., 2015, 13, 11096
    DOI: 10.1039/C5OB01729G

Search articles by author

Spotlight

Advertisements