1E7-03, a low MW compound targeting host protein phosphatase-1, inhibits HIV-1 transcription
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 Q35VCF38 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.
Ammosova, Tatyana; Platonov, Maxim; Ivanov, Andrei; Kont, Yasemin Saygideʇer; Kumari, Namita; Kehn-Hall, Kylene; Jerebtsova, Marina; Kulkarni, Amol A.; Üren, Aykut; Kovalskyy, Dmytro; and Nekhai, Sergei, "1E7-03, a low MW compound targeting host protein phosphatase-1, inhibits HIV-1 transcription" (2014). The Center For Sickle Cell Disease Faculty Publications. 64.