Enhancing the ligand efficiency of anti-HIV compounds targeting frameshift-stimulating RNA. Issue 13 (1st July 2019)

• Record Type: Journal Article
• Authors: Anokhina, Viktoriya S.; McAnany, John D.; Ciesla, Jessica H.; Hilimire, Thomas A.; Santoso, Netty; Miao, Hongyu; Miller, Benjamin L.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 27:Issue 13(2019)
• Page Start: 2972
• Page End: 2977
• Publication Date: 2019-07-01
• Subjects: Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2019.05.009
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Ribosomal frameshifting, a process whereby a translating ribosome is diverted from one reading frame to another on a contiguous mRNA, is an important regulatory mechanism in biology and an opportunity for therapeutic intervention in several human diseases. In HIV, ribosomal frameshifting controls the ratio of Gag and Gag-Pol, two polyproteins critical to the HIV life cycle. We have previously reported compounds able to selectively bind an RNA stemloop within the Gag-Pol mRNA; these compounds alter the production of Gag-Pol in a manner consistent with increased frameshifting. Importantly, they also display antiretroviral activity in human T -cells. Here, we describe new compounds with significantly reduced molecular weight, but with substantially maintained affinity and anti-HIV activity. These results suggest that development of more "ligand efficient" enhancers of ribosomal frameshifting is an achievable goal.