Effect of each guanidinium group on the RNA recognition and cellular uptake of Tat-derived peptides.
The six arginine (Arg) residues in the human immunodeficiency virus transactivator of transcription protein (HIV Tat protein) basic region (residues 47-57) are crucial for two bioactivities: RNA recognition and cellular uptake. Herein, we report a systematic study to investigate the role of the guanidinium group on Arg at each position in Tat-derived peptides for the two bioactivities. Tat-derived peptides, in which each guanidinium-bearing arginine was replaced with a urea-bearing citrulline (Cit) or an ammonium-bearing Lys, were synthesized by solid phase peptide synthesis. RNA recognition of the peptides was studied by electrophoretic mobility shift assays, and cellular uptake into Jurkat cells was determined by flow cytometry. Our results showed that removing the positive charge and altering the hydrogen bonding capacity of Arg affect the two biological functions differently. Furthermore, the effects are position dependent. These findings should be useful for the development of functional molecules containing guanidinium, urea, and 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.
Cheng-Hsun
CH
Wu
Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan.
Ming-Huei
MH
Weng
Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan.
Hsien-Chen
HC
Chang
Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan.
Jhe-Hao
JH
Li
Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan. Electronic address: rpcheng@ntu.edu.tw.
Richard P
RP
Cheng
D005434:Flow Cytometry; D019791:Guanidine / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; 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; D019791:Guanidine
Arginine; Cellular uptake; Guanidinium group; RNA recognition; Tat-derived peptide