NMR-based identification of peptides that specifically recognize the d-arm of tRNA.
Human tRNA3(Lys) is used by HIV virus as a primer for the reverse transcription of its genome. The 18 nucleotides at the 3'-end of the tRNA3(Lys) are hybridized to a complementary sequence of the viral RNA called the primer-binding site. A screen against the human tRNA3(Lys) over a peptide library designed to target RNA has been performed. Of the 175 hexapeptides tested, three were found to bind to the d-stem of tRNA3(Lys). Alanine-scanning was used to define the determinants of the interaction between the peptides and tRNA3(Lys). They also bind to two other tested tRNAs, also at the level of the d-stem and loop, although the nucleotide sequence of the stem differs in one of them. These short peptides thus recognize specific structural features within the d-stem and loop of tRNAs. Associated with other pharmacophores, they could be useful to design optimized ligands targeting specific tRNAs such as retroviral replication primers.
Tisné
Carine
C
Laboratoire de Cristallographie et RMN Biologiques, UMR 8015 CNRS/Université Paris 5, Faculté de Pharmacie, 4 avenue de l'Observatoire, 75006 Paris, France. carine.tisne@univ-paris5.fr
Guillière
Florence
F
Dardel
Frédéric
F
D001665:Binding Sites; D017931:DNA Primers; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008024:Ligands; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D009690:Nucleic Acid Conformation; D019151:Peptide Library; D010455:Peptides / Q000378:metabolism*; D012343:RNA, Transfer / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D048348:Reverse Transcription
D017931:DNA Primers; D008024:Ligands; D019151:Peptide Library; D010455:Peptides; D012343:RNA, Transfer