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Medicinal-Pharmaceutical Chemistry Commons

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Chemistry Publications

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Articles 1 - 19 of 19

Full-Text Articles in Medicinal-Pharmaceutical Chemistry

Rapid Characterization Of Formulated Pharmaceuticals Using Fast Mas 1h Solid-State Nmr Spectroscopy, David A. Hirsh, Anuradha V. Wijesekara, Scott L. Carnahan, Ivan Hung, Joseph W. Lubach, Karthik Nagapudi, Aaron J. Rossini May 2019

Rapid Characterization Of Formulated Pharmaceuticals Using Fast Mas 1h Solid-State Nmr Spectroscopy, David A. Hirsh, Anuradha V. Wijesekara, Scott L. Carnahan, Ivan Hung, Joseph W. Lubach, Karthik Nagapudi, Aaron J. Rossini

Chemistry Publications

Active pharmaceutical ingredients (APIs) can be prepared in many different solid forms and phases that affect their physicochemical properties and suitability for oral dosage forms. The development and commercialization of dosage forms require analytical techniques that can determine and quantify the API phase in the final drug product. 13C solid-state NMR (SSNMR) spectroscopy is widely employed to characterize pure and formulated solid APIs; however, 13C SSNMR experiments on dosage forms with low API loading are often challenging due to low sensitivity and interference from excipients. Here, fast MAS 1H SSNMR experiments are shown to be applicable for the rapid characterization ...


Defining Cell Cluster Size By Dielectrophoretic Capture At An Array Of Wireless Electrodes Of Several Distinct Lengths, Joseph T. Banovetz, Min Li, Darshna Pagariya, Sungu Kim, Baskar Ganapathysubramanian, Robbyn Anand Apr 2019

Defining Cell Cluster Size By Dielectrophoretic Capture At An Array Of Wireless Electrodes Of Several Distinct Lengths, Joseph T. Banovetz, Min Li, Darshna Pagariya, Sungu Kim, Baskar Ganapathysubramanian, Robbyn Anand

Chemistry Publications

Clusters of biological cells play an important role in normal and disease states, such as in the release of insulin from pancreatic islets and in the enhanced spread of cancer by clusters of circulating tumor cells. We report a method to pattern cells into clusters having sizes correlated to the dimensions of each electrode in an array of wireless bipolar electrodes (BPEs). The cells are captured by dielectrophoresis (DEP), which confers selectivity, and patterns cells without the need for physical barriers or adhesive interactions that can alter cell function. Our findings demonstrate that this approach readily achieves fine control of ...


Nanoparticle Microarray For High-Throughput Microbiome Metabolomics Using Matrix-Assisted Laser Desorption Ionization Mass Spectrometry, Rebecca L. Hansen, Maria Emilia Duenas, Torey Looft, Young Jin Lee Oct 2018

Nanoparticle Microarray For High-Throughput Microbiome Metabolomics Using Matrix-Assisted Laser Desorption Ionization Mass Spectrometry, Rebecca L. Hansen, Maria Emilia Duenas, Torey Looft, Young Jin Lee

Chemistry Publications

A high-throughput matrix-assisted laser desorption/ionization mass spectrometry (MALDI)-MS-based metabolomics platform was developed using a pre-fabricated microarray of nanoparticles and organic matrices. Selected organic matrices, inorganic nanoparticle (NP) suspensions, and sputter coated metal NPs, as well as various additives, were tested for metabolomics analysis of the turkey gut microbiome. Four NPs and one organic matrix were selected as the optimal matrix set: α-cyano-4-hydroycinnamic acid, Fe3O4 and Au NPs in positive ion mode with 10 mM sodium acetate, and Cu and Ag NPs in negative ion mode with no additive. Using this set of five matrices, over two thousand unique ...


Indole Anion Cycloadditions With Methyl Coumalate, George A. Kraus, Huangchao Yu Feb 2018

Indole Anion Cycloadditions With Methyl Coumalate, George A. Kraus, Huangchao Yu

Chemistry Publications

The reaction of the anion of indoles with methyl coumalate followed by selective opening of the lactone led to the preparation of tricyclic intermediates for indole alkaloid synthesis.


Poly(Ethyl Glyoxylate)-Poly(Ethylene Oxide) Nanoparticles: Stimuli- Responsive Drug Release Via End-To-End Polyglyoxylate Depolymerization, Bo Fan, Elizabeth Gillies Mar 2017

Poly(Ethyl Glyoxylate)-Poly(Ethylene Oxide) Nanoparticles: Stimuli- Responsive Drug Release Via End-To-End Polyglyoxylate Depolymerization, Bo Fan, Elizabeth Gillies

Chemistry Publications

The ability to disrupt polymer assemblies in response to specifi c stimuli provides the potential to release drugs selectively at certain sites or conditions in vivo. However, most stimuli-responsive delivery systems require many stimuli initiated events to release drugs. Self-immolative polymers offer the potential to provide amplifi ed responses to stimuli as they undergo complete end-to-end depolymerization following the cleavage of a single end-cap. Herein, linker end-caps were developed to conjugate self-immolative poly(ethyl glyoxylate) (PEtG) with poly(ethylene oxide) (PEO) to form amphiphilic block copolymers. These copolymers were self-assembled to form nanoparticles in aqueous solution. Cleavage of the linker ...


Synthesis, Self-Assembly, And Immunological Activity Of Α-Galactose-Functionalized Dendron–Lipid Amphiphiles, John Trant, Namrata Jain, D. M. Mazzuca, J Trevor Mcintosh, Bo Fan, S M Mansour Haeryfar, Sebastien Lecommandoux, Elizabeth Gillies Sep 2016

Synthesis, Self-Assembly, And Immunological Activity Of Α-Galactose-Functionalized Dendron–Lipid Amphiphiles, John Trant, Namrata Jain, D. M. Mazzuca, J Trevor Mcintosh, Bo Fan, S M Mansour Haeryfar, Sebastien Lecommandoux, Elizabeth Gillies

Chemistry Publications

Nanoassemblies presenting multivalent displays of biologically active carbohydrates are of significant interest for a wide array of biomedical applications ranging from drug delivery to immunotherapy. In this study, glycodendronlipid hybrids were developed as a new and tunable class of dendritic amphiphiles. A modular synthesis was used to prepare dendronlipid hybrids comprising distearylglycerol and 0 through 4th generation polyester dendrons with peripheral protected amines. Following deprotection of the amines, an isothiocyanate derivative of C-linked α-galactose (α-Gal) was conjugated to the dendron peripheries, affording amphiphiles with 1 to 16 α-Gal moieties. Self-assembly in water through a ...


The Role Of A Conserved Membrane Proximal Cysteine In Altering Αps2cβps Integrin Diffusion, Aleem Syed, Neha Arora, Thomas A. Bunch, Emily A. Smith Jan 2016

The Role Of A Conserved Membrane Proximal Cysteine In Altering Αps2cβps Integrin Diffusion, Aleem Syed, Neha Arora, Thomas A. Bunch, Emily A. Smith

Chemistry Publications

Cysteine residues (Cys) in the membrane proximal region are common post-translational modification (PTM) sites in transmembrane proteins. Herein, the effects of a highly conserved membrane proximal α-subunit Cys1368 on the diffusion properties of αPS2CβPS integrins are reported. Sequence alignment shows that this cysteine is palmitoylated in human α3 and α6 integrin subunits. Replacing Cys1368 in wild-type integrins with valine (Val1368) putatively blocks a PTM site and alters integrins' ligand binding and diffusion characteristics. Both fluorescence recovery after photobleaching (FRAP) and single particle tracking (SPT) diffusion measurements show Val1368 integrins are more mobile compared to ...


Heterocycles From Wine: Synthesis And Biological Evaluation Of Salidrosides, Tezcan Guney, Stephanie A. Kohles, Victoria L. Thompson, Gregory J. Phillips, George A. Kraus May 2015

Heterocycles From Wine: Synthesis And Biological Evaluation Of Salidrosides, Tezcan Guney, Stephanie A. Kohles, Victoria L. Thompson, Gregory J. Phillips, George A. Kraus

Chemistry Publications

Wine is composed of a variety of tannins, of which a sub-class includes salidrosides, which are largely uninvestigated compounds. The first syntheses of galloylated salidrosides are reported in 7 steps from commercially available starting materials through a platform approach. The antimicrobial activity of the salidrosides against Escherichia coli strains is described.


Application Of Scanning Angle Raman Spectroscopy For Determining The Location Of Buried Polymer Interfaces With Tens Of Nanometer Precision, Craig A. Damin, Vy H.T. Nguyen, Auguste S. Niyibizi, Emily A. Smith Jan 2015

Application Of Scanning Angle Raman Spectroscopy For Determining The Location Of Buried Polymer Interfaces With Tens Of Nanometer Precision, Craig A. Damin, Vy H.T. Nguyen, Auguste S. Niyibizi, Emily A. Smith

Chemistry Publications

Near-infrared scanning angle (SA) Raman spectroscopy was utilized to determine the interface location in bilayer films (a stack of two polymer layers) of polystyrene (PS) and polycarbonate (PC). Finite-difference-time-domain (FDTD) calculations of the sum square electric field (SSEF) for films with total bilayer thicknesses of 1200–3600 nm were used to construct models for simultaneously measuring the film thickness and the location of the buried interface between the PS and PC layers. Samples with total thicknesses of 1320, 1890, 2300, and 2750 nm and varying PS/PC interface locations were analyzed using SA Raman spectroscopy. Comparing SA Raman spectroscopy and ...


Upgrading Malic Acid To Bio-Based Benzoates Via A Diels–Alder-Initiated Sequence With The Methyl Coumalate Platform, Jennifer J. Lee, Gerald R. Pollock Iii, Donald Mitchell, Lindsay Kasuga, George A. Kraus Sep 2014

Upgrading Malic Acid To Bio-Based Benzoates Via A Diels–Alder-Initiated Sequence With The Methyl Coumalate Platform, Jennifer J. Lee, Gerald R. Pollock Iii, Donald Mitchell, Lindsay Kasuga, George A. Kraus

Chemistry Publications

The conversion of naturally-occurring malic acid to the 2-pyrone methyl coumalate was optimized using a variety of acid catalysts. Coupling methyl coumalate with electron-rich dienophiles in an inverse electron-demand Diels–Alder (IEDDA)/decarboxylation/elimination domino sequence resulted in an investigation of the scope and limitations of the methodology. The thermal, metal-free, and one-pot procedure allows regioselective access to diverse aromatic compounds including tricyclic, biphenyl, and pyridinyl systems for elaboration. A comparison with analogous pyrones demonstrates the striking efficacy of methyl coumalate as a versatile platform for the generation of biorenewable functionalized benzoates.


Near Ir Scanning Angle Total Internal Reflection Raman Spectroscopy At Smooth Gold Films, Kristopher J. Mckee, Matthew W. Meyer, Emily A. Smith Apr 2012

Near Ir Scanning Angle Total Internal Reflection Raman Spectroscopy At Smooth Gold Films, Kristopher J. Mckee, Matthew W. Meyer, Emily A. Smith

Chemistry Publications

Total internal reflection (TIR) Raman and reflectivity spectra were collected for nonresonant analytes as a function of incident angle at sapphire or sapphire/smooth 50 nm gold interfaces using 785 nm excitation. For both interfaces, the Raman signal as a function of incident angle is well-modeled by the calculated interfacial mean square electric field (MSEF) relative to the incident field times the thickness of the layer being probed in the Raman measurement (DRS). The Raman scatter was reproducibly enhanced at the interface containing a gold film relative to the sapphire interface by a factor of 4.3−4.6 for ...


Membrane-Dependent Effects Of A Cytoplasmic Helix On The Structure And Drug Binding Of The Influenza Virus M2 Protein, Sarah D. Cady, Tuo Wang, Mei Hong Jun 2011

Membrane-Dependent Effects Of A Cytoplasmic Helix On The Structure And Drug Binding Of The Influenza Virus M2 Protein, Sarah D. Cady, Tuo Wang, Mei Hong

Chemistry Publications

The influenza A M2 protein forms a proton channel for virus infection and also mediates virus assembly and budding. The minimum protein length that encodes both functions contains the transmembrane (TM) domain (roughly residues 22–46) for the amantadine-sensitive proton-channel activity and an amphipathic cytoplasmic helix (roughly residues 45–62) for curvature induction and virus budding. However, structural studies involving the TM domain with or without the amphipathic helix differed on the drug-binding site. Here we use solid-state NMR spectroscopy to determine the amantadine binding site in the cytoplasmic-helix-containing M2(21–61). 13C–2H distance measurements of 13C-labeled protein and ...


Specific Binding Of Adamantane Drugs And Direction Of Their Polar Amines In The Pore Of The Influenza M2 Transmembrane Domain In Lipid Bilayers And Dodecylphosphocholine Micelles Determined By Nmr Spectroscopy, Sarah D. Cady, Jun Wang, Yibing Wu, William F. Degrado, Mei Hong Mar 2011

Specific Binding Of Adamantane Drugs And Direction Of Their Polar Amines In The Pore Of The Influenza M2 Transmembrane Domain In Lipid Bilayers And Dodecylphosphocholine Micelles Determined By Nmr Spectroscopy, Sarah D. Cady, Jun Wang, Yibing Wu, William F. Degrado, Mei Hong

Chemistry Publications

The transmembrane domain of the influenza M2 protein (M2TM) forms a tetrameric proton channel important for the virus lifecycle. The proton-channel activity is inhibited by amine-containing adamantyl drugs amantadine and rimantadine, which have been shown to bind specifically to the pore of M2TM near Ser31. However, whether the polar amine points to the N- or C-terminus of the channel has not yet been determined. Elucidating the polar group direction will shed light on the mechanism by which drug binding inhibits this proton channel and will facilitate rational design of new inhibitors. In this study, we determine the polar amine direction ...


Conformational Plasticity Of The Influenza A M2 Transmembrane Helix In Lipid Bilayers Under Varying Ph, Drug Binding, And Membrane Thickness, Fanghao Hu, Wenbin Luo, Sarah D. Cady, Mei Hong Jan 2011

Conformational Plasticity Of The Influenza A M2 Transmembrane Helix In Lipid Bilayers Under Varying Ph, Drug Binding, And Membrane Thickness, Fanghao Hu, Wenbin Luo, Sarah D. Cady, Mei Hong

Chemistry Publications

Membrane proteins change their conformations to respond to environmental cues, thus conformational plasticity is important for function. The influenza A M2 protein forms an acid-activated proton channel important for the virus lifecycle. Here we have used solid-state NMR spectroscopy to examine the conformational plasticity of membrane-bound transmembrane domain of M2 (M2TM). 13C and 15N chemical shifts indicate coupled conformational changes of several pore-facing residues due to changes in bilayer thickness, drug binding, and pH. The structural changes are attributed to the formation of a well-defined helical kink at G34 in the drug-bound state and in thick lipid bilayers, nonideal backbone ...


Development Of A Scanning Angle Total Internal Reflection Raman Spectrometer, Kristopher J. Mckee, Emily A. Smith Apr 2010

Development Of A Scanning Angle Total Internal Reflection Raman Spectrometer, Kristopher J. Mckee, Emily A. Smith

Chemistry Publications

A scanning angle total internal reflection (SATIR) Raman spectrometer has been developed for measuring interfacial phenomena with chemical specificity and high axial resolution perpendicular to the interface. The instrument platform is an inverted optical microscope with added automated variable angle optics to control the angle of an incident laser on a prism/sample interface. These optics include two motorized translation stages, the first containing a focusing lens and the second a variable angle galvanometer mirror. The movement of all instrument components is coordinated to ensure that the same sample location and area are probed at each angle. At angles greater ...


Structure Of The Amantadine Binding Site Of Influenza M2 Proton Channels In Lipid Bilayers, Sarah D. Cady, Klaus Schmidt-Rohr, Jun Wang, Cinque S. Soto, William F. Degrado, Mei Hong Feb 2010

Structure Of The Amantadine Binding Site Of Influenza M2 Proton Channels In Lipid Bilayers, Sarah D. Cady, Klaus Schmidt-Rohr, Jun Wang, Cinque S. Soto, William F. Degrado, Mei Hong

Chemistry Publications

The M2 protein of influenza A virus is a membrane-spanning tetrameric proton channel targeted by the antiviral drugs amantadine and rimantadine1. Resistance to these drugs has compromised their effectiveness against many influenza strains, including pandemic H1N1. A recent crystal structure of M2(22–46) showed electron densities attributed to a single amantadine in the amino-terminal half of the pore2, indicating a physical occlusion mechanism for inhibition. However, a solution NMR structure of M2(18–60) showed four rimantadines bound to the carboxy-terminal lipid-facing surface of the helices3, suggesting an allosteric mechanism. Here we show by solid-state NMR ...


Structure And Function Of The Influenza A M2 Proton Channel, Sarah D. Cady, Wenbin Luo, Fanghao Hu, Mei Hong Jun 2009

Structure And Function Of The Influenza A M2 Proton Channel, Sarah D. Cady, Wenbin Luo, Fanghao Hu, Mei Hong

Chemistry Publications

The M2 protein of influenza A viruses forms a tetrameric pH-activated proton-selective channel that is targeted by the amantadine class of antiviral drugs. Its ion channel function has been extensively studied by electrophysiology and mutagenesis; however, the molecular mechanism of proton transport is still elusive, and the mechanism of inhibition by amantadine is controversial. We review the functional data on proton channel activity, molecular dynamics simulations of the proton conduction mechanism, and high-resolution structural and dynamical information of this membrane protein in lipid bilayers and lipid-mimetic detergents. These studies indicate that elucidation of the structural basis of M2 channel activity ...


General In Vivo Assay For The Study Of Integrin Cell Membrane Receptor Microclustering, Emily A. Smith, Thomas A. Bunch, Danny L. Brower Mar 2007

General In Vivo Assay For The Study Of Integrin Cell Membrane Receptor Microclustering, Emily A. Smith, Thomas A. Bunch, Danny L. Brower

Chemistry Publications

A method for measuring the microclustering of a class of cell surface receptors called integrins is reported. Integrins are proteins involved in bidirectional signaling across the cell membrane and are important in cell adhesion, growth, and survival. Their activity is regulated by changes in protein conformation and protein clustering. The developed in vivo clustering assay uses fluorescence resonance energy transfer (FRET) and has the benefit of requiring a single cloning step to generate FRET donors and acceptors that can be used to measure the clustering of a series of integrin mutants. The FRET reporters contain extracellular donor or acceptor fluorescent ...


Light-Induced Acidification By The Antiviral Agent Hypericin, Michael J. Fehr, M. A. Mccloskey, Jacob W. Petrich Feb 1995

Light-Induced Acidification By The Antiviral Agent Hypericin, Michael J. Fehr, M. A. Mccloskey, Jacob W. Petrich

Chemistry Publications

The naturally occurring polycyclic quinone hypericin possesses light-induced antiviral activity against the human immunodeficiency virus (HIV) and other closely related enveloped lentiviruses such as equine infectious anemia virus (EIAV). We have previously argued that hypericin undergoes a fast proton transfer reaction in its singlet state (J. Phys. Chem. 1994, 98, 5784). We have also presented evidence that the light-induced antiviral activity of hypericin does not depend upon the formation of singlet oxygen (Bioorg. Med. Chem. Lett. 1994, 4, 1339). It is demonstrated here that steady-state illumination of a solution containing hypericin effects a pH drop. When hypericin and an indicator ...