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

Ammosova, YASEMİN; Platonov, Maxim; Ivanov, Andrei; Kont, Yasemin; Kumari, Namita; Kehn-Hall, Kylene; Jerebtsova, Marina; Kulkarni, Amol; Ueren, Aykut; Kovalskyy, Dmytro; Nekhai, Sergei

doi:10.1111/bph.12863

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

Ammosova T., Platonov M., Ivanov A., Kont Y. S., Kumari N., Kehn-Hall K., ...Daha Fazla

BRITISH JOURNAL OF PHARMACOLOGY, cilt.171, sa.22, ss.5059-5075, 2014 (SCI-Expanded, Scopus)

Yayın Türü: Makale / Tam Makale
Cilt numarası: 171 Sayı: 22
Basım Tarihi: 2014
Doi Numarası: 10.1111/bph.12863
Dergi Adı: BRITISH JOURNAL OF PHARMACOLOGY
Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
Sayfa Sayıları: ss.5059-5075
Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
Çukurova Üniversitesi Adresli: Hayır

Özet

Background and PurposeHIV-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.