Effect of lysine methylation and acetylation on the RNA recognition and cellular uptake of Tat-derived peptides.
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.
Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan.
Mu-Chun
MC
Liu
Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan.
Chin-Yih
CY
Chen
Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan.
Chang-Hwa
CH
Chiang
Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan.
Wei-Ming
WM
Wang
Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan. Electronic address: rpcheng@ntu.edu.tw.
Richard P
RP
Cheng
D000107:Acetylation; D006801:Humans; D006860:Hydrogen Bonding; D019169:Jurkat Cells; D008239:Lysine / Q000737:chemistry / Q000378:metabolism*; D008745:Methylation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000378:metabolism*
D010455:Peptides; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus; D008239:Lysine
Acetylation; Cellular uptake; Lysine; Methylation; RNA recognition; Tat-derived peptide