1E7-03, a low MW compound targeting host protein phosphatase-1, inhibits HIV-1 transcription.

ABSTRACT:

Background and purpose

HIV-1 transcription is activated by the Tat protein which recruits the cyclin-dependent kinase CDK9/cyclin T1 to TAR RNA. Tat binds to protein phosphatase-1 (PP1) through the Q(35) VCF(38) sequence and translocates PP1 to the nucleus. PP1 dephosphorylates CDK9 and activates HIV-1 transcription. We have synthesized a low MW compound 1H4, that targets PP1 and prevents HIV-1 Tat interaction with PP1 and inhibits HIV-1 gene transcription. Here, we report our further work with the 1H4-derived compounds and analysis of their mechanism of action.

Experimental approach

Using the 1H4-PP1 complex as a model, we iteratively designed and synthesized follow-up libraries that were analysed for the inhibition of HIV-1 transcription and toxicity. We also confirmed the

SUBMITTER: Ammosova T 

PROVIDER: S-EPMC4253456 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature