TAR-RNA BINDING BY HIV-1 TAT PROTEIN IS SELECTIVELY INHIBITED BY ITS L-ENANTIOMER

An oligoribonucleotide, corresponding to the Tat-interactive top half of the HIV-1 TAR RNA stem-loop, was synthesized in both the natural D- and the enantiomeric L-configurations. The affinity of Tat for the tw o RNAs, assessed by competition binding experiments, was found to be i dentical and is reduced 10-fold for both, upon replacement of the crit ical bulge residue U23 with cytidine, it is suggested that this intera ction of the flexible Tat protein depends strongly upon the tertiary s tructure of a binding pocket within TAR, but not upon its handedness, and may be described by a 'hand-in-mitten' model.