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Articles 1 - 5 of 5
Full-Text Articles in Medicine and Health Sciences
Anticancer Properties Of Distinct Antimalarial Drug Classes, Rob Hooft Van Huijsduijnen, R. Kiplin Guy, Kelly Chibale, Richard K. Haynes, Ingmar Peitz, Gerhard Kelter, Margaret A. Phillips, Jonathan L. Vennerstrom, Yongyuth Yuthavong, Timothy N. C. Wells
Anticancer Properties Of Distinct Antimalarial Drug Classes, Rob Hooft Van Huijsduijnen, R. Kiplin Guy, Kelly Chibale, Richard K. Haynes, Ingmar Peitz, Gerhard Kelter, Margaret A. Phillips, Jonathan L. Vennerstrom, Yongyuth Yuthavong, Timothy N. C. Wells
Journal Articles: Pharmaceutical Sciences
We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase) inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase) and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin …
Mechanism Of Amyloid Β-Protein Dimerization Determined Using Single-Molecule Afm Force Spectroscopy., Zhengjian Lv, Robin Roychaudhuri, Margaret M. Condron, David B. Teplow, Yuri L. Lyubchenko
Mechanism Of Amyloid Β-Protein Dimerization Determined Using Single-Molecule Afm Force Spectroscopy., Zhengjian Lv, Robin Roychaudhuri, Margaret M. Condron, David B. Teplow, Yuri L. Lyubchenko
Journal Articles: Pharmaceutical Sciences
Aβ42 and Aβ40 are the two primary alloforms of human amyloid β-protein (Aβ). The two additional C-terminal residues of Aβ42 result in elevated neurotoxicity compared with Aβ40, but the molecular mechanism underlying this effect remains unclear. Here, we used single-molecule force microscopy to characterize interpeptide interactions for Aβ42 and Aβ40 and corresponding mutants. We discovered a dramatic difference in the interaction patterns of Aβ42 and Aβ40 monomers within dimers. Although the sequence difference between the two peptides is at the C-termini, the N-terminal segment plays a key role in the peptide interaction in the dimers. This is an unexpected finding …
Mechanism Of Amyloid Β-Protein Dimerization Determined Using Single-Molecule Afm Force Spectroscopy., Zhengjian Lv, Robin Roychaudhuri, Margaret M Condron, David B. Teplow, Yuri L. Lyubchenko
Mechanism Of Amyloid Β-Protein Dimerization Determined Using Single-Molecule Afm Force Spectroscopy., Zhengjian Lv, Robin Roychaudhuri, Margaret M Condron, David B. Teplow, Yuri L. Lyubchenko
Journal Articles: Pharmaceutical Sciences
Aβ42 and Aβ40 are the two primary alloforms of human amyloid β-protein (Aβ). The two additional C-terminal residues of Aβ42 result in elevated neurotoxicity compared with Aβ40, but the molecular mechanism underlying this effect remains unclear. Here, we used single-molecule force microscopy to characterize interpeptide interactions for Aβ42 and Aβ40 and corresponding mutants. We discovered a dramatic difference in the interaction patterns of Aβ42 and Aβ40 monomers within dimers. Although the sequence difference between the two peptides is at the C-termini, the N-terminal segment plays a key role in the peptide interaction in the dimers. This is an unexpected finding …
A Dexamethasone Prodrug Reduces The Renal Macrophage Response And Provides Enhanced Resolution Of Established Murine Lupus Nephritis, Fang Yuan, Dana Tabor, Richard K. Nelson, Hongjiang Yuan, Yijia Zhang, Jenny Nuxoll, Kimberly K. Bynote, Subodh M. Lele, Dong Wang, Karen A. Gould
A Dexamethasone Prodrug Reduces The Renal Macrophage Response And Provides Enhanced Resolution Of Established Murine Lupus Nephritis, Fang Yuan, Dana Tabor, Richard K. Nelson, Hongjiang Yuan, Yijia Zhang, Jenny Nuxoll, Kimberly K. Bynote, Subodh M. Lele, Dong Wang, Karen A. Gould
Journal Articles: Pharmaceutical Sciences
We evaluated the ability of a macromolecular prodrug of dexamethasone (P-Dex) to treat lupus nephritis in (NZB × NZW)F1 mice. We also explored the mechanism underlying the anti-inflammatory effects of this prodrug. P-Dex eliminated albuminuria in most (NZB × NZW)F1 mice. Furthermore, P-Dex reduced the incidence of severe nephritis and extended lifespan in these mice. P-Dex treatment also prevented the development of lupus-associated hypertension and vasculitis. Although P-Dex did not reduce serum levels of anti-dsDNA antibodies or glomerular immune complexes, P-Dex reduced macrophage recruitment to the kidney and attenuated tubulointerstitial injury. In contrast to what was observed with free dexamethasone, …
Crystal Structure Of 3wj Core Revealing Divalent Ion-Promoted Thermostability And Assembly Of The Phi29 Hexameric Motor Prna., Hui Zhang, James A. Endrizzi, Yi Shu, Farzin Haque, Claude Sauter, Luda S. Shlyakhtenko, Yuri L. Lyubchenko, Peixuan Guo, Young-In Chi
Crystal Structure Of 3wj Core Revealing Divalent Ion-Promoted Thermostability And Assembly Of The Phi29 Hexameric Motor Prna., Hui Zhang, James A. Endrizzi, Yi Shu, Farzin Haque, Claude Sauter, Luda S. Shlyakhtenko, Yuri L. Lyubchenko, Peixuan Guo, Young-In Chi
Journal Articles: Pharmaceutical Sciences
The bacteriophage phi29 DNA packaging motor, one of the strongest biological motors characterized to date, is geared by a packaging RNA (pRNA) ring. When assembled from three RNA fragments, its three-way junction (3WJ) motif is highly thermostable, is resistant to 8 M urea, and remains associated at extremely low concentrations in vitro and in vivo. To elucidate the structural basis for its unusual stability, we solved the crystal structure of this pRNA 3WJ motif at 3.05 Å. The structure revealed two divalent metal ions that coordinate 4 nt of the RNA fragments. Single-molecule fluorescence resonance energy transfer (smFRET) analysis confirmed …