Enhancing the ligand efficiency of anti-HIV compounds targeting frameshift-stimulating RNA |
| |
Authors: | Viktoriya S Anokhina John D McAnany Jessica H Ciesla Thomas A Hilimire Netty Santoso Hongyu Miao Benjamin L Miller |
| |
Institution: | 1. Department of Biochemistry and Biophysics, University of Rochester, Rochester, NY 14642, United States;2. Department of Chemistry, University of Rochester, Rochester, NY 14642, United States;3. Department of Dermatology, University of Rochester, Rochester, NY 14642, United States;4. Department of Biostatistics, University of Rochester, Rochester, NY 14642, United States;5. Department of Biostatistics and Data Science, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, United States |
| |
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. |
| |
Keywords: | Corresponding author |
本文献已被 ScienceDirect 等数据库收录! |
|