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Medicinal-Pharmaceutical Chemistry Commons

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Medicine and Health Sciences

2015

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Articles 31 - 38 of 38

Full-Text Articles in Medicinal-Pharmaceutical Chemistry

Development Of A Novel Screening Strategy Designed To Discover A New Class Of Hiv Drugs, Nancy Cheng, Sook-Kyung Lee, P. Donover, Mel Reichman, Celia Schiffer, Emily Hull-Ryde, Ronald Swanstrom, William Janzen Jan 2015

Development Of A Novel Screening Strategy Designed To Discover A New Class Of Hiv Drugs, Nancy Cheng, Sook-Kyung Lee, P. Donover, Mel Reichman, Celia Schiffer, Emily Hull-Ryde, Ronald Swanstrom, William Janzen

Celia A. Schiffer

Current antiretroviral treatments target multiple pathways important for human immunodeficiency virus (HIV) multiplication, including viral entry, synthesis and integration of the DNA provirus, and the processing of viral polyprotein precursors. However, HIV is becoming increasingly resistant to these "combination therapies." Recent findings show that inhibition of HIV Gag protein cleavage into its two structural proteins, matrix (MA) and capsid (CA), has a devastating effect on viral production, revealing a potential new target class for HIV treatment. Unlike the widely used HIV protease inhibitors, this new class of inhibitor would target the substrate, not the protease enzyme itself. This approach offers ...


Gold Nanoparticles Stabilized With Mpeg-Grafted Poly(L-Lysine): In Vitro And In Vivo Evaluation Of A Potential Theranostic Agent, Alexei A. Bogdanov, Suresh Gupta, Nadezhda Koshkina, Stuart J. Corr, Surong Zhang, Steven A. Curley, Gang Han Jan 2015

Gold Nanoparticles Stabilized With Mpeg-Grafted Poly(L-Lysine): In Vitro And In Vivo Evaluation Of A Potential Theranostic Agent, Alexei A. Bogdanov, Suresh Gupta, Nadezhda Koshkina, Stuart J. Corr, Surong Zhang, Steven A. Curley, Gang Han

Radiology Publications and Presentations

As the number of diagnostic and therapeutic applications utilizing gold nanoparticles (AuNPs) increases, so does the need for AuNPs that are stable in vivo, biocompatible, and suitable for bioconjugation. We investigated a strategy for AuNP stabilization that uses methoxypolyethylene glycol-graft-poly(l-lysine) copolymer (MPEG-gPLL) bearing free amino groups as a stabilizing molecule. MPEG-gPLL injected into water solutions of HAuCl4 with or without trisodium citrate resulted in spherical (Zav = 36 nm), monodisperse (PDI = 0.27), weakly positively charged nanoparticles (AuNP3) with electron-dense cores (diameter: 10.4 +/- 2.5 nm) and surface amino groups that were amenable to covalent modification. The AuNP3 were ...


Large Interdomain Rearrangement Triggered By Suppression Of Micro- To Millisecond Dynamics In Bacterial ​Enzyme I, Vincenzo Venditti, Vitali Tugarinov, Charles D. Schwieters, Alexander Grishaev, G. Marius Clore Jan 2015

Large Interdomain Rearrangement Triggered By Suppression Of Micro- To Millisecond Dynamics In Bacterial ​Enzyme I, Vincenzo Venditti, Vitali Tugarinov, Charles D. Schwieters, Alexander Grishaev, G. Marius Clore

Vincenzo Venditti

Enzyme I (EI), the first component of the bacterial phosphotransfer signal transduction system, undergoes one of the largest substrate-induced interdomain rearrangements documented to date. Here we characterize the perturbations generated by two small molecules, the natural substrate phosphoenolpyruvate and the inhibitor a-ketoglutarate, on the structure and dynamics of EI using NMR, small-angle X-ray scattering and biochemical techniques. The results indicate unambiguously that the open-to-closed conformational switch of EI is triggered by complete suppression of micro- to millisecond dynamics within the C-terminal domain of EI. Indeed, we show that a ligand-induced transition from a dynamic to a more rigid conformational state ...


Stability Of Lidocaine Tested By Forced Degradation And Its Interactions With Serum Albumin, Lindsay Nichols Jan 2015

Stability Of Lidocaine Tested By Forced Degradation And Its Interactions With Serum Albumin, Lindsay Nichols

STAR (STEM Teacher and Researcher) Presentations

A concern for future long-term manned space expeditions is the ability to treat illnesses with appropriate pharmaceuticals. However, pharmaceuticals degrade faster in space than on Earth presumably due to an abundance of space radiation. The stability of Lidocaine was investigated because it is a common pain reliever currently used on the International Space Station. One of the most common proteins in blood is serum albumin, which acts as a carrier to distribute drugs throughout the body. It is important to know how well the drug binds to serum albumin so that the rate of distribution of Lidocaine-bound protein in blood ...


Specific N-Glycans Of Hepatocellular Carcinoma Cell Surface And The Abnormal Increase Of Core-Α-1, 6-Fucosylated Triantennary Glycan Via N-Acetylglucosaminyltransferases-Iva Regulation, Huan Nie, Xia Liu, Yubao Zhang, Tingting Li, Chao Zhan, Wenjuan Huo, Anshun He, Yuanfei Yao, Yu Jin, Youpeng Qu, Xue-Long Sun, Yu Li Jan 2015

Specific N-Glycans Of Hepatocellular Carcinoma Cell Surface And The Abnormal Increase Of Core-Α-1, 6-Fucosylated Triantennary Glycan Via N-Acetylglucosaminyltransferases-Iva Regulation, Huan Nie, Xia Liu, Yubao Zhang, Tingting Li, Chao Zhan, Wenjuan Huo, Anshun He, Yuanfei Yao, Yu Jin, Youpeng Qu, Xue-Long Sun, Yu Li

Chemistry Faculty Publications

Glycosylation alterations of cell surface proteins are often observed during the progression of malignancies. The specific cell surface N-glycans were profiled in hepatocellular carcinoma (HCC) with clinical tissues (88 tumor and adjacent normal tissues) and the corresponding serum samples of HCC patients. The level of core-α-1,6-fucosylated triantennary glycan (NA3Fb) increased both on the cell surface and in the serum samples of HCC patients (p < 0.01). Additionally, the change of NA3Fb was not influenced by Hepatitis B virus (HBV)and cirrhosis. Furthermore, the mRNA and protein expression of N-acetylglucosaminyltransferase IVa (GnT-IVa), which was related to the synthesis of the NA3Fb, was substantially increased in HCC tissues. Knockdown of GnT-IVa leads to a decreased level of NA3Fb and decreased ability of invasion and migration in HCC cells. NA3Fb can be regarded as a specific cell surface N-glycan of HCC. The high expression of GnT-IVa is the cause of the abnormal increase of NA3Fb on the HCC cell surface, which regulates cell migration. This study demonstrated the specific N-glycans of the cell surface and the mechanisms of altered glycoform related with HCC. These findings lead to better understanding of the function of glycan and glycosyltransferase in the tumorigenesis, progression and metastasis of HCC.


Synthesis And Characterization Of Imidazolium Salt Derivatives For Anti-Tumor Activity, Ryan W. Pearce Jan 2015

Synthesis And Characterization Of Imidazolium Salt Derivatives For Anti-Tumor Activity, Ryan W. Pearce

Williams Honors College, Honors Research Projects

Several aldehydes (butanal, pentanal, hexanal, 4-hydroxybenzaldehyde) were reacted with 1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (1) to produce novel C2 substituted imidazolium salts for the potential use against non-small cell lung cancer in humans. Compounds 2-(1-hydroxypentyl)-1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (3) and 2-(1-hydroxyhexyl)-1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (5) were successfully synthesized with structures supported by NMR and mass spectrometry. Characterization by 1H NMR showed evidence of 1 in both compounds. The tumor cell growth inhibition of 3 against non-small cell lung cancer lines NCI-A549, NCI-H460, HCC827, and NCI-H1975 was tested and found to be comparable ...


Total Synthesis Of Biologically Active Natural And Unnatural Products, Julia Heimberger Jan 2015

Total Synthesis Of Biologically Active Natural And Unnatural Products, Julia Heimberger

Electronic Theses and Dissertations

Herbarin A and B were isolated from the fungal strains of Cladosporium herbarum found in marine sponges Aplysina aerophoba and Callyspongia aerizusa. Total synthesis of Herbarin A and B was achieved by carrying out a multi-step synthesis approach, and the antioxidant properties were evaluated using FRAP assay. Toxicity of these compounds was determined using a zebrafish embryo model. Furthermore, synthesis of C-6 alkyl-azaarene derivatives of nucleosides by Csp3-H bond functionalization were investigated. Effective incorporation of 2-methylazaarene moiety at the C-6 position of the protected inosine nucleoside provided a new class of compounds with anticipated enhanced biological activity.


Design, Synthesis, And Pharmacological Evaluation Of Three Series Of Lobelane Analogs As Inhibitors Of The Vesicular Monoamine Transporter (Vmat2), John P. Culver Jan 2015

Design, Synthesis, And Pharmacological Evaluation Of Three Series Of Lobelane Analogs As Inhibitors Of The Vesicular Monoamine Transporter (Vmat2), John P. Culver

Theses and Dissertations--Pharmacy

Methamphetamine (METH) abuse is a serious problem in the United States and worldwide. The reward experienced by METH users is due to the increase in extracellular dopamine (DA) concentrations caused by an interaction between METH and the DA transporter (DAT) as well as the Vesicular Monoamine Transporter-2 (VMAT2). The reward felt by users of METH leads to further use of the drug and subsequent abuse. The current project examined the ability of three novel series of lobelane analogs to interact with a binding site on the Vesicular Monoamine Transporter-2 (VMAT2) in an attempt to inhibit the effects of METH. Lobelane ...