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Full-Text Articles in Medical Molecular Biology
Complex Interplay Of Kinetic Factors Governs The Synergistic Properties Of Hiv-1 Entry Inhibitors., Koree W. Ahn, Michael J. Root
Complex Interplay Of Kinetic Factors Governs The Synergistic Properties Of Hiv-1 Entry Inhibitors., Koree W. Ahn, Michael J. Root
Department of Biochemistry and Molecular Biology Faculty Papers
The homotrimeric HIV-1 envelope glycoprotein (Env) undergoes receptor-triggered structural changes that mediate viral entry through membrane fusion. This process is inhibited by chemokine receptor antagonists (CoRAs) that block Env-receptor interactions and by fusion inhibitors (FIs) that disrupt Env conformational transitions. Synergy between CoRAs and FIs has been attributed to a CoRA-dependent decrease in the rate of viral membrane fusion that extends the lifetime of the intermediate state targeted by FIs. Here, we demonstrated that the magnitude of CoRA/FI synergy unexpectedly depends on FI-binding affinity and the stoichiometry of chemokine receptor binding to trimeric Env. For C-peptide FIs (clinically represented by …
Dysregulated Gpcr Signaling And Therapeutic Options In Uveal Melanoma., Vivian Chua, Dominic Lapadula, Clinita Randolph, Jeffrey L. Benovic, Philip B. Wedegaertner, Andrew E. Aplin
Dysregulated Gpcr Signaling And Therapeutic Options In Uveal Melanoma., Vivian Chua, Dominic Lapadula, Clinita Randolph, Jeffrey L. Benovic, Philip B. Wedegaertner, Andrew E. Aplin
Department of Biochemistry and Molecular Biology Faculty Papers
Uveal melanoma is the most common primary intraocular malignant tumor in adults and arises from the transformation of melanocytes in the uveal tract. Even after treatment of the primary tumor, up to 50% of patients succumb to metastatic disease. The liver is the predominant organ of metastasis. There is an important need to provide effective treatment options for advanced stage uveal melanoma. To provide the preclinical basis for new treatments, it is important to understand the molecular underpinnings of the disease. Recent genomic studies have shown that mutations within components of G protein-coupled receptor (GPCR) signaling are early events associated …