RNA as a target for drug design, the example of Tat-TAR interaction

• Published in: Current topics in medicinal chemistry Vol. 2; no. 10; p. 1123
• Main Authors: Froeyen, M, Herdewijn, P
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.10.2002
• Subjects: Anti-HIV Agents - chemistry; Drug Design; Gene Products, tat - antagonists & inhibitors; Gene Products, tat - metabolism; HIV Long Terminal Repeat - drug effects; Humans; Intercalating Agents - chemistry; Intercalating Agents - pharmacology; Intercalating Agents - therapeutic use; Oligonucleotides, Antisense - chemistry; Oligonucleotides, Antisense - pharmacology; Oligonucleotides, Antisense - therapeutic use; Peptides - chemistry; Peptides - pharmacology; Peptides - therapeutic use; RNA, Viral - antagonists & inhibitors; RNA, Viral - metabolism; Structure-Activity Relationship
• ISSN: 1568-0266
• DOI: 10.2174/1568026023393200

One of the new targets in the battle against HIV-1 infection is the interaction between the viral transactivator and the transactivation response (TAR) element, which is necessary for HIV-1 replication. After an overview of the most recent structural studies of the Tat-TAR system, new TAR-targeted inhibitors are presented in several classes: antisense oligonucleotides, cationic peptides, intercalators and a large class of small RNA binding molecules. The method of library screening of RNA binding ligands in the search for new inhibitors is explained in detail. Inhibition of Tat-TAR interaction is considered as a realistic approach to develop new anti-HIV compounds. The RNA binding molecules in this review also demonstrate that the development of drugs that target RNA will become a feasible goal and that such compounds will be added in the future to the therapeutic arsenal to combat several diseases.