An ultra-high affinity ligand of HIV-1 TAR reveals the RNA structure recognized by P-TEFb.

ABSTRACT: The HIV-1 trans-activator protein Tat binds the trans-activation response element (TAR) to facilitate recruitment of the super elongation complex (SEC) to enhance transcription of the integrated pro-viral genome. The Tat-TAR interaction is critical for viral replication and the emergence of the virus from the latent state, therefore, inhibiting this interaction has long been pursued to discover new anti-viral or latency reversal agents. However, discovering active compounds that directly target RNA with high affinity and selectivity remains a significant challenge; limiting pre-clinical development. Here, we report the rational design of a macrocyclic peptide mimic of the arginine rich motif of Tat, which binds to TAR with low pM affinity and 100-fold selectivity against closely homologous

SUBMITTER: Shortridge MD 

PROVIDER: S-EPMC6379670 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature