Effect of lysine methylation and acetylation on the RNA recognition and cellular uptake of Tat-derived peptides

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• 作者：Mu-Chun Liu ; Chin-Yih Chen ; Chang-Hwa Chiang ; Wei-Ming Wang ; Richard P. Cheng ; ^{rpcheng@ntu.edu.tw" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Tat-derived peptide ; Lysine ; Methylation ; Acetylation ; RNA recognition ; Cellular uptake
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：1 November 2016
• 年：2016
• 卷：24
• 期：21
• 页码：5047-5051
• 全文大小：538 K

文摘

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.