Pharmacy and Pharmaceutical Sciences Commons^™

Design And Development Of A Novel Class Of Cell Cycle Cdk Inhibitors Targeting The Cyclin Binding Groove Utilizing The Replace Strategy, Padmavathy Nandha Premnath

Theses and Dissertations

Inhibition of CDK2 activity in G1 and S phases of the cell cycle can promote selective apoptosis of cancer cells through the E2F1 pathway. Currently available CDK inhibitors target the ATP binding pocket and result in lack of specificity for the cell cycle vs. the transcriptional CDKs. It has been shown that a peptide HAKRRLIF derived from the tumor suppressor p21 binds to the cyclin binding groove (CBG) and selectively inhibits cell cycle CDKs (CDK2/Cyclin A, CDK2/Cyclin E and CDK4/Cyclin D). The CBG is unique to cell cycle CDKs hence targeting this site avoids the inhibition of transcriptional CDKs can …

Effects Of Hiv-1 Tat Protein On Structure, Function And Trafficking Of The Dopamine Transporter, Narasimha Murty Midde

Theses and Dissertations

The alarming rise in HIV-1 associated neurocognitive disorder (HAND) is, at least in part, associated with HIV-1 viral proteins shed from infected macrophages, including transactivator of transcription (Tat) despite the success of anti-retroviral therapies. The dopamine (DA) system is greatly involved in the progression of HAND and is influenced by psychostimulants like cocaine. The DA transporter (DAT), a key regulator of neurocognitive functions, is a major molecular target for both Tat and cocaine. Our lab previously reported that exposure to Tat decreases DA uptake through allosteric regulation and alters cocaine binding sites in DAT.

In this research project the hypothesis …