The positively charged residues arginine (Arg) and lysine (Lys) are important for RNA binding. Single mutants of the HIV Tat-derived peptide, in which the side chain length of the positively charged residues were altered one at a time, were evaluated for specific TAR RNA binding by electrophoresis mobility shift assay. Based on this data, a series of Tat-derived peptides incorporating Arg and Lys analogs with mixed side chain lengths was designed for high specific binding to TAR RNA. These peptides with mixed side chain lengths for the positively charged residues exhibited higher TAR RNA binding specificity, enhanced cellular uptake efficiency, and increased resistance toward trypsin compared to the native ArgTat peptide (containing Arg and Lys). Importantly, all designed peptides suppressed Tat-dependent luciferase expression more than the wild type ArgTat. These results suggest that altering the positively charged residues side chain length is a viable strategy to simultaneously enhance multiple biological functions and ultimately protein expression.

Attenuating HIV Tat-mediated protein expression by exploiting positively charged amino acids side chain length

248th National Meeting (2014)

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