INHIBITORS OF PROTEIN-RNA COMPLEXATION THAT TARGET THE RNA - SPECIFICRECOGNITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TAR RNA BY SMALL ORGANIC-MOLECULES
Hy. Mei et al., INHIBITORS OF PROTEIN-RNA COMPLEXATION THAT TARGET THE RNA - SPECIFICRECOGNITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TAR RNA BY SMALL ORGANIC-MOLECULES, Biochemistry (Easton), 37(40), 1998, pp. 14204-14212
TAR RNA represents an attractive target for the intervention of human
immunodeficiency virus type 1 (HIV-1) replication by small molecules.
We now describe three small molecule inhibitors of the HIV-1 Tat-TAR i
nteraction that target the RNA, not the protein. The chemical structur
es and RNA binding characteristics of these inhibitors are unique for
each molecule. Results from various biochemical and spectroscopic meth
ods reveal that each of the three Tat-TAR inhibitors recognizes a diff
erent structural feature at the bulge, lower stem, or loop region of T
AR. Furthermore, one of these Tat-TAR inhibitors has been demonstrated
, in cellular environments, to inhibit (a) a TAR-dependent, Tat activa
ted transcription and (b) the replication of HIV-1 in a latently infec
tious model.