Effect of lysine methylation and acetylation on the RNA recognition and cellular uptake of Tat-derived peptides
Journal
Bioorganic and Medicinal Chemistry
Journal Volume
24
Journal Issue
21
Pages
5047-5051
Date Issued
2016
Author(s)
Abstract
The two lysine (Lys) residues in the human immunodeficiency virus trans-activator of transcription protein (HIV Tat protein) basic region (residues 47–57) are crucial for two bioactivities: RNA recognition and cellular uptake. Since the post-translational modifications of these two Lys residues affect the biological function of the Tat protein, we investigated the effect of methylation and acetylation of Lys50 and Lys51 in Tat-derived peptides on the two bioactivities. Tat-derived peptides, in which each lysine was replaced with a methylated- or acetylated-Lys, were synthesized by solid phase peptide synthesis. TAR RNA recognition of the peptides was studied by electrophoretic mobility shift assays. Cellular uptake of the peptides into Jurkat cells was determined by flow cytometry. Our results showed that acetylation of either Lys residue attenuated both bioactivities. In contrast, the effect of Lys methylation on the bioactivities depended on position and number of methyl groups. These findings should be useful for the development of functional molecules containing ammonium groups for RNA recognition to affect biological processes and for cellular uptake for drug delivery. ? 2016 Elsevier Ltd
Subjects
Acetylation; Cellular uptake; Lysine; Methylation; RNA recognition; Tat-derived peptide
SDGs
Other Subjects
ammonia; lysine; transactivator protein; lysine; peptide; transactivator protein; virus RNA; Article; controlled study; drug delivery system; enzyme activity; flow cytometry; gel mobility shift assay; jurkat cell line; limit of quantitation; nonhuman; protein acetylation; protein methylation; protein processing; protein synthesis; RNA analysis; RNA binding; RNA recognition; acetylation; chemistry; human; hydrogen bond; Jurkat cell line; metabolism; methylation; synthesis; Acetylation; Humans; Hydrogen Bonding; Jurkat Cells; Lysine; Methylation; Peptides; RNA, Viral; tat Gene Products, Human Immunodeficiency Virus
Type
journal article