LNA derivatives of a kissing aptamer targeted to the trans-activating responsive RNA element of HIV-1.
We previously identified an RNA aptamer targeted to the trans-activating responsive (TAR) element of the HIV-1 genome [F. Ducongé, J.J. Toulmé, In vitro selection identifies key determinants for loop--loop interactions: RNA aptamers selective for the TAR RNA element of HIV--1. RNA 5 (1999) 1605--1614]. This hairpin aptamer binds to its target through loop-loop interactions. We derived chemically modified R06 aptamers that show improved nuclease resistance and affinity for TAR. We review here the results obtained with chimeric aptamers containing locked nucleic acid (LNA) residues. Chimeras containing 2 to 4 LNA residues in an RNA or 2'-O-methyl,RNA context display binding properties of interest and compete with the viral protein Tat for binding to TAR. NMR studies have shown that these properties are modulated by the conformation of the loop-loop helix depending on the presence of LNA residues.
Lebars
Isabelle
I
UMR CNRS 5144, Institut Européen de Chimie et Biologie, Pessac, France.
Richard
Tristan
T
Di Primo
Carmelo
C
Toulmé
Jean-Jacques
JJ
D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000235:genetics; D020029:Base Pairing; D001665:Binding Sites; D015696:Gene Products, tat; D016679:Genome, Viral; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000235:genetics; D054322:tat Gene Products, Human Immunodeficiency Virus
D052157:Aptamers, Nucleotide; D015696:Gene Products, tat; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; C477371:locked nucleic acid; D054322:tat Gene Products, Human Immunodeficiency Virus