INHIBITORS OF PROTEIN-RNA COMPLEXATION THAT TARGET THE RNA - SPECIFICRECOGNITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TAR RNA BY SMALL ORGANIC-MOLECULES

Citation
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
Citations number
44
Categorie Soggetti
Biology
Journal title
ISSN journal
00062960
Volume
37
Issue
40
Year of publication
1998
Pages
14204 - 14212
Database
ISI
SICI code
0006-2960(1998)37:40<14204:IOPCTT>2.0.ZU;2-P
Abstract
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.