34 results on '"Jerry Yang"'
Search Results
2. Relationship between severity scoring indices and time-interval of ICU escalation in an obstetric transport population
- Author
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Emad Elsamadicy, Jerry Yang, Vainavi Gambhir, Saad Pirzada, Anya Plotnikova, Manahel Zahid, Quincy Tran, and Allison Lankford
- Subjects
Obstetrics and Gynecology - Published
- 2023
3. The utility of severity scoring systems to identify obstetric transports at risk for ICU escalation
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Emad Elsamadicy, Anya Plotnikova, Jerry Yang, Vainavi Gambhir, Manahel Zahid, Saad Pirzada, Quincy Tran, and Allison Lankford
- Subjects
Obstetrics and Gynecology - Published
- 2023
4. Evaluation of tetraether lipid-based liposomal carriers for encapsulation and retention of nucleoside-based drugs
- Author
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Takaoki Koyanagi, Geoffray Leriche, Valentina Paolucci, and Jerry Yang
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0301 basic medicine ,Drug ,Membrane permeability ,media_common.quotation_subject ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Polar surface area ,Structure-Activity Relationship ,03 medical and health sciences ,Drug Delivery Systems ,Cell Line, Tumor ,Drug Discovery ,Humans ,Lipid bilayer ,Molecular Biology ,Cell Proliferation ,media_common ,Drug Carriers ,Liposome ,Chromatography ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,Organic Chemistry ,Nucleosides ,Lipids ,0104 chemical sciences ,030104 developmental biology ,Membrane ,Liposomes ,Drug delivery ,Lipophilicity ,Molecular Medicine ,Drug Screening Assays, Antitumor - Abstract
Although liposomal nanoparticles are one of the most versatile class of drug delivery systems, stable liposomal formulation of small neutral drug molecules still constitutes a challenge due to the low drug retention of current lipid membrane technologies. In this study, we evaluate the encapsulation and retention of seven nucleoside analog-based drugs in liposomes made of archaea-inspired tetraether lipids, which are known to enhance packing and membrane robustness compared to conventional bilayer-forming lipids. Liposomes comprised of the pure tetraether lipid generally showed improved retention of drugs (up to 4-fold) compared with liposomes made from a commercially available diacyl lipid. Interestingly, we did not find a significant correlation between the liposomal leakage rates of the molecules with typical parameters used to assess lipophilicity of drugs (such logD or topological polar surface area), suggesting that specific structural elements of the drug molecules can have a dominant effect on leakage from liposomes over general lipophilic character.
- Published
- 2017
5. Temperature-Controlled Single-Liposome Proton Permeability Assay of Extremophile-Inspired Lipid Membranes
- Author
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Jerry Yang, Geoffray Leriche, Michael Mayer, Thomas Schroeder, Anirvan Guha, and Melissa L. McGuire
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Liposome ,Membrane ,Chemistry ,Permeability (electromagnetism) ,Biophysics ,Extremophile - Published
- 2019
6. Artificial Membrane Attack Complex through DNA-Guided Self-Assembly of Pore-Forming Peptides: Biological Nanopores with Programmable Diameter
- Author
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Simon Finn Mayer, Jonathan List, Sandra Rodriguez Gonzalo, Julie Ducrey, Michael Mayer, Frederick Bertani, Laura Pascual, Aziz Fennouri, and Jerry Yang
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Nanopore ,chemistry.chemical_compound ,Materials science ,chemistry ,Biophysics ,Synthetic membrane ,Self-assembly ,DNA - Published
- 2019
7. Self-assembled, cation-selective ion channels from an oligo(ethylene glycol) derivative of benzothiazole aniline
- Author
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Kevin D. Lance, Michael Mayer, Panchika Prangkio, Mark Rubinshtein, Divya K. Rao, and Jerry Yang
- Subjects
Spectrometry, Mass, Electrospray Ionization ,Magnetic Resonance Spectroscopy ,Stereochemistry ,Membrane permeable ,Biophysics ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Ion Channels ,03 medical and health sciences ,chemistry.chemical_compound ,Aniline ,Antibiotics ,Cations ,Cell Line, Tumor ,Polymer chemistry ,Self-assembled ion channel ,Humans ,Moiety ,Benzothiazoles ,Lipid bilayer ,030304 developmental biology ,0303 health sciences ,Bilayer ,Benzothiazole aniline ,Cell Biology ,Oligo(ethylene glycol) ,0104 chemical sciences ,Biosensors ,Monomer ,chemistry ,Benzothiazole ,Gramicidin ,Ethylene Glycols ,Ethylene glycol - Abstract
This paper describes the spontaneous formation of well-defined pores in planar lipid bilayers from the self-assembly of a small synthetic molecule that contains a benzothiazole aniline (BTA) group attached to a tetra-ethylene glycol (EG4) moiety. Macroscopic and single-channel current recordings suggest that these pores are formed by the assembly of four BTA-EG4 monomers with an open pore diameter that appears similar to the one of gramicidin pores (~ 0.4 nm). The single-channel conductance of these pores is modulated by the pH of the electrolyte and has a minimum at pH ~ 3. Self-assembled pores from BTA-EG4 are selective for monovalent cations and have long open channel lifetimes on the order of seconds. BTA-EG4 monomers in these pores appear to be arranged symmetrically across both leaflets of the bilayer, and spectroscopy studies suggest that the fluorescent BTA group is localized inside the lipid bilayers. In terms of biological activity, BTA-EG4 molecules inhibited growth of gram-positive Bacillus subtilis bacteria (IC50 ~ 50 μM) and human neuroblastoma SH-SY5Y cells (IC50 ~ 60 μM), while they were not toxic to gram-negative Escherichia coli bacteria at a concentration up to 500 μM. Based on these properties, this drug-like, synthetic, pore-forming molecule with a molecular weight below 500 g mol− 1 might be appealing as a starting material for development of antibiotics or membrane-permeating moieties for drug delivery. From a biophysical point of view, long-lived, well-defined ion-selective pores from BTA-EG4 molecules offer an example of a self-assembled synthetic supramolecule with biological function.
- Published
- 2011
8. Amyloid-binding Small Molecules Efficiently Block SEVI (Semen-derived Enhancer of Virus Infection)- and Semen-mediated Enhancement of HIV-1 Infection
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Stephen Dewhurst, Bradley L. Nilsson, Jerry Yang, Rajesh K. Srivastava, Caitlin Brown, Christina C. Capule, Joanna S. Olsen, Mark Rubinshtein, Changyong Feng, and Todd M. Doran
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Male ,Amyloid ,Sexual transmission ,Microbicide ,Virus Attachment ,Plasma protein binding ,Biology ,Microbiology ,Antiviral Agents ,Biochemistry ,Jurkat cells ,Virus ,Jurkat Cells ,03 medical and health sciences ,Virus Infection ,Semen ,Cell Line, Tumor ,Animals ,Humans ,Benzothiazoles ,Molecular Biology ,Cells, Cultured ,030304 developmental biology ,0303 health sciences ,Dose-Response Relationship, Drug ,Molecular Structure ,030306 microbiology ,Virion ,HIV ,Cell Biology ,Flow Cytometry ,Small molecule ,Competitive Bidding ,3. Good health ,Cell biology ,Kinetics ,Thiazoles ,Prostatic acid phosphatase ,SEVI ,HIV-1 ,Human Immunodeficiency Virus ,Protein Binding - Abstract
Semen was recently shown to contain amyloid fibrils formed from a self-assembling peptide fragment of the protein prostatic acid phosphatase. These amyloid fibrils, termed semen-derived enhancer of virus infection, or SEVI, have been shown to strongly enhance HIV infectivity and may play an important role in sexual transmission of HIV, making them a potential microbicide target. One novel approach to target these fibrils is the use of small molecules known to intercalate into the structure of amyloid fibrils, such as derivatives of thioflavin-T. Here, we show that the amyloid-binding small molecule BTA-EG(6) (the hexa(ethylene glycol) derivative of benzothiazole aniline) is able to bind SEVI fibrils and effectively inhibit both SEVI-mediated and semen-mediated enhancement of HIV infection. BTA-EG(6) also blocks the interactions of SEVI with HIV-1 virions and HIV-1 target cells but does not cause any inflammation or toxicity to cervical epithelial cells. These results suggest that an amyloid-binding small molecule may have utility as a microbicide, or microbicidal supplement, for HIV-1.
- Published
- 2010
9. Applications of biological pores in nanomedicine, sensing, and nanoelectronics
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Jerry Yang, Erik Yusko, Michael Mayer, Sheereen Majd, Yazan N. Billeh, and Michael X. Macrae
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Chemistry ,Biomedical Engineering ,Bioengineering ,Nanotechnology ,Article ,Single strand dna ,Nanopore ,Nanomedicine ,Membrane ,Nanoelectronics ,Drug delivery ,Biophysics ,Nanobiotechnology ,Electronics ,Flux (metabolism) ,Biotechnology - Abstract
Biological protein pores and pore-forming peptides can generate a pathway for the flux of ions and other charged or polar molecules across cellular membranes. In nature, these nanopores have diverse and essential functions that range from maintaining cell homeostasis and participating in cell signaling to activating or killing cells. The combination of the nanoscale dimensions and sophisticated - often regulated - functionality of these biological pores make them particularly attractive for the growing field of nanobiotechnology. Applications range from single-molecule sensing to drug delivery and targeted killing of malignant cells. Potential future applications may include the use of nanopores for single strand DNA sequencing and for generating bio-inspired, and possibly, biocompatible visual detection systems and batteries. This article reviews the current state of applications of pore-forming peptides and proteins in nanomedicine, sensing, and nanoelectronics.
- Published
- 2010
10. An EEL-Inspired Artificial Electric Organ: 110 Volts from Water and Salt
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Anirvan Guha, Aaron Lamoureux, Michael Mayer, David Sept, Max Shtein, Jerry Yang, Gloria VanRenterghem, and Thomas Schroeder
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0301 basic medicine ,chemistry.chemical_classification ,Materials science ,Electric organ ,Inorganic chemistry ,Biophysics ,Salt (chemistry) ,Volt ,02 engineering and technology ,021001 nanoscience & nanotechnology ,03 medical and health sciences ,030104 developmental biology ,chemistry ,0210 nano-technology - Published
- 2018
11. Biophysical Characterization of Lipid Membranes: Effect of Lipid Head Groups and Tails on Synthetic and Natural Lipid Membranes
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Young Hun Kim, Joon H. Lee, Ratnash Lal, and Jerry Yang
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Membrane ,Chemistry ,Biophysics ,Head (vessel) - Published
- 2018
12. Inhibiting protein–amyloid interactions with small molecules: A surface chemistry approach
- Author
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Jerry Yang and Petra Inbar
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Amyloid ,Surface Properties ,Clinical Biochemistry ,Pharmaceutical Science ,Enzyme-Linked Immunosorbent Assay ,macromolecular substances ,Fibril ,Biochemistry ,chemistry.chemical_compound ,Amyloid disease ,Drug Discovery ,Benzothiazoles ,Molecular Biology ,chemistry.chemical_classification ,Molecular Structure ,Chemistry ,Organic Chemistry ,Proteins ,Small molecule ,Thiazoles ,Surface coating ,Immunoglobulin G ,Acridines ,Molecular Medicine ,Thioflavin ,Glycoprotein ,Proflavine ,Intracellular ,Protein Binding - Abstract
This paper presents a surface-based approach to inhibit the binding of proteins to Alzheimer's-related beta-amyloid (Abeta) fibrils with small molecules. It reports the idea of using an intracellular, disease-related fibril as a material whose surface can be coated with small molecules. Using an ELISA-based assay, molecular surface coatings with thioflavin T are shown to inhibit 65+/-10% of the binding of two different anti-Abeta IgGs to Abeta fibrils. A molecular surface coating with 3,6-diamino acridine was able to inhibit 76+/-10% of the binding of an anti-Abeta IgG to Abeta fibrils. Maximal inhibition of these protein-amyloid interactions appears in the low to mid-micromolar range of small molecule. This demonstration that molecular surface coatings can be used to attenuate the interaction of proteins with these fibrils suggests a potentially new strategy for therapeutics in neurodegenerative amyloid diseases.
- Published
- 2006
13. Biomimetic hydroxylation of saturated carbons with artificial cytochrome P-450 enzymes—liberating chemistry from the tyranny of functional groups
- Author
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Ronald Breslow, Jiaming Yan, and Jerry Yang
- Subjects
chemistry.chemical_classification ,Double bond ,Cytochrome ,biology ,Organic Chemistry ,Biochemistry ,Cytochrome P-450 Enzymes ,Catalysis ,Hydroxylation ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,biology.protein ,Organic chemistry ,Reactivity (chemistry) - Abstract
Five mimics of cytochrome P-450 have been prepared and examined as catalysts for the specific hydroxylation of steroids. Reactions occur dictated by the geometries of the complexes, overcoming the intrinsic reactivity of a carbon–carbon double bond and of a secondary carbinol group. In some cases as many as 3000 catalytic turnovers are observed.
- Published
- 2002
14. Archaeal-Inspired Lipids Exhibit Low Membrane Permeability due to Entropic Effects
- Author
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Takaoki Koyanagi, Young Hun Kim, Michael Mayer, David Sept, Karthikeyan Diraviyam, Thomas Schroeder, Jerry Yang, Olivia M. Eggenberger, and Geoffray Leriche
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Membrane ,Chromatography ,Membrane permeability ,Chemical physics ,Chemistry ,Covalent bond ,Bilayer ,Monolayer ,Biophysics ,Entropy of activation ,Permeation ,Material properties - Abstract
Many archaea are able to withstand extremes of temperature, pressure, pH and/or levels of salt. One unique feature of these extremophiles that gives them this capability is that their membranes are made from covalently linked, tetraether lipids that form a monolayer rather than a traditional bilayer. Here we present experimental and computational results on a series of synthetic archaeal-inspired lipids, looking at their biophysical properties and rates of permeation. Apart from a number of interesting mechanical and material properties, we find that tethered lipids exhibit a much stronger dependence on the entropy of activation for small molecules to cross the membrane. In relating our measured permeation rates with properties of the membrane, we find that the order parameters for the lipid tails describe the changes in entropy, and the combination of area per lipid, membrane thickness and short-range diffusion coefficient can predict our permeation results. Interestingly, we also see that the rates of water penetration into the core of the membrane provide an excellent empirical measure that matches our experimental permeation rates.
- Published
- 2017
15. Broadly Accessible Assays with Signal Amplification across Lipid Bilayers
- Author
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Jerry Yang, Sarah Grunsfeld, Thomas Schroeder, Michael Mayer, and Anirvan Guha
- Subjects
Analyte ,Membrane ,Chemistry ,Bilayer ,fungi ,Biophysics ,Molecule ,Nanotechnology ,Lipid bilayer ,Electrochemical gradient ,Flux (metabolism) ,Ion channel - Abstract
Over the past decade, droplet interface bilayers (DIBs) have emerged as a robust platform for performing studies across lipid membranes with the potential for high-throughput applications. Here we explore the potential of DIBs for detecting the presence of analytes in a heterogeneous sample without the need for an external power source. We discuss the formation of DIBs by a broadly accessible and straightforward pipetting step leading to stable DIBs between two aqueous reservoirs with a proton gradient across the bilayer interface. When a pore-forming peptide is present, the pH of the reservoirs change, which can be detected by the unaided eye based on the color change of a pH sensitive dye. This approach takes advantage of bio-inspired amplification in the sense that one ion channel, after analyte-triggered activation, facilitates the flux of thousands of ions across the DIB. We describe our attempts to impede H+/OH- flux using known pore blockers in order to detect alterations in the rate of color change in the presence of these molecules. We also discuss the possibility of using pore-forming peptides engineered to alter their function in the presence of a specific analyte in order to detect this analyte within a sample. Our ultimate goal is to develop an assay to screen samples of biofluids in a broadly-accessible and robust manner that can be adapted to various analytes and biomarkers.
- Published
- 2017
16. Targeting Specific Membranes with the Pore-Forming Peptide Ceratotoxin a using Click Chemistry
- Author
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Jerry Yang, Aziz Fennouri, Simon Finn Mayer, and Michael Mayer
- Subjects
chemistry.chemical_classification ,Membrane ,chemistry ,Biophysics ,Click chemistry ,Peptide ,Combinatorial chemistry - Published
- 2017
17. An Exploration into the Optimal Lipid Coating for Nanopore-Based Protein Characterization
- Author
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Brandon R. Bruhn, Olivia M. Eggenberger, Michael Mayer, Jerry Yang, Haiyan Liu, and Geoffray Leriche
- Subjects
Nanopore ,Materials science ,Coating ,Biophysics ,engineering ,Nanotechnology ,engineering.material ,Characterization (materials science) - Published
- 2017
18. An Electric Eel-Inspired Origami-Enabled Battery that Generates 100 V
- Author
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Max Shtein, Anirvan Guha, Michael Mayer, Jerry Yang, Thomas Schroeder, and Aaron Lamoureux
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Battery (electricity) ,Engineering ,biology ,business.industry ,Biophysics ,Electrical engineering ,Automotive battery ,biology.organism_classification ,business ,Electric eel - Published
- 2017
19. An Ion Channel Platform for Detection of Small Molecule Analytes
- Author
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Leibniz Hang, Jerry Yang, Young Hun Kim, and Michael Mayer
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chemistry.chemical_classification ,Analyte ,Electrophysiology ,Membrane ,Chromatography ,chemistry ,Biophysics ,Gramicidin A ,Peptide ,Small molecule ,Ion channel ,Ion - Abstract
The development of detection assays for small molecule analytes based on ion channel proteins makes it possible to exploit the amplification properties of membrane pores in response to specific external stimuli. Here, we used C-terminal derivatives of an ion channel-forming peptide, gramicidin A (gA), to explore an ion channel-based method for monitoring environmental contamination such as toxins or lethal microorganisms. Our initial results suggest that the modified ion channel-forming peptides can respond to a range of tailored, external, small molecule stimuli to produce detectable changes in electrophysiological properties.
- Published
- 2014
- Full Text
- View/download PDF
20. Regioselective oxidations of equilenin derivatives catalyzed by a rhodium(III) porphyrin complex—contrast with the manganese(III) porphyrin
- Author
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Ronald Breslow and Jerry Yang
- Subjects
inorganic chemicals ,Iodosobenzene ,organic chemicals ,Organic Chemistry ,chemistry.chemical_element ,Regioselectivity ,Manganese ,Biochemistry ,Porphyrin ,Medicinal chemistry ,Rhodium ,Catalysis ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,medicine ,Organic chemistry ,heterocyclic compounds ,Equilenin ,Selectivity ,medicine.drug - Abstract
Equilenin acetate and dihydroequilenin acetate were oxidized with iodosobenzene and a rhodium(III) porphyrin catalyst. The selectivity of the reactions differs from that with the corresponding Mn(III) catalyst, or from that of free radical chain oxidation.
- Published
- 2000
21. A Systematic Investigation to Determine the Optimal Lipid Coating for Nanopore-Based Sensing Experiments
- Author
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Geoffray Leriche, Haiyan Liu, Brandon R. Bruhn, Jerry Yang, Olivia M. Eggenberger, and Michael Mayer
- Subjects
Crystallography ,Chemistry ,Membrane lipids ,Bilayer ,Peripheral membrane protein ,Biophysics ,lipids (amino acids, peptides, and proteins) ,Biological membrane ,Lipid bilayer phase behavior ,Model lipid bilayer ,Lipid bilayer ,Elasticity of cell membranes - Abstract
Despite the importance of proteins, nanopore sensing has so far been mostly focused on single molecule DNA and RNA characterization. One factor that limited experiments with proteins were nonspecific interactions of proteins with the walls of synthetic nanopores. We showed recently, that nanopores with fluid coatings of phospholipid bilayers circumvented this problem. In addition, anchoring proteins to lipid anchors slowed down protein translocation through nanopores and enabled determination of parameters such as the shape, volume, and dipole moment of individual non-spherical proteins. To slow down the translocation time of lipid-anchored proteins further, we have recently formed highly viscous coatings from archaea-inspired lipids. These synthetic lipids are composed of two hydrophilic head groups connected by a long hydrophobic chain; each head group is also attached to an acyl chain that spans half of the membrane thickness. As these lipids contain -in one molecule- the components of a typical lipid bilayer, a single layer is sufficient to form a stable membrane. Experimentation with many lipid coatings, including a variety of archaea-inspired lipids, has revealed differences in translocation of protein, bilayer stability and event frequency. Every bilayer composition tested has been designed to optimize each of these characteristics.
- Published
- 2015
22. Proton Permeation through Extremophile-Inspired Lipid Membranes
- Author
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Michael Mayer, Geoffray Leriche, Mitchell A. Johnson, Takaoki Koyanagi, Kathryn N. Haengel, Thomas Schroeder, Jerry Yang, and Claire L. Wang
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Liposome ,biology ,Chemistry ,Chemical structure ,Biophysics ,Context (language use) ,Ether ,Permeation ,biology.organism_classification ,chemistry.chemical_compound ,Membrane ,Structural motif ,Archaea - Abstract
The cell membranes of thermoacidophilic archaea contain lipids with unique structural motifs such as ether linkages, branched chains, and membrane-spanning bipolar macrocycles that may allow the organisms to maintain the large pH gradient they require to survive. We investigated the relationship between the chemical structure of a number of lipids and the proton permeability of the membranes they form by using an optimized proton permeation assay performed on liposomes containing a fluorescent indicator dye. This work focuses on the effects of tethering on proton permeability and examines lipids with membrane-spanning chains of varied length and chemical structure (e.g. number and identity of rings). We discuss the results in the context of similar chemical groups and structures found in the cell membranes of extremophiles.
- Published
- 2015
- Full Text
- View/download PDF
23. Geometrically directed selective steroid hydroxylation with high turnover by a fluorinated artificial cytochrome P-450
- Author
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Jerry Yang, Ronald Breslow, and Bartolo Gabriele
- Subjects
Cytochrome ,biology ,Stereochemistry ,medicine.medical_treatment ,Organic Chemistry ,Biochemistry ,Porphyrin ,Steroid ,carbohydrates (lipids) ,Hydroxylation ,chemistry.chemical_compound ,chemistry ,mental disorders ,Drug Discovery ,polycyclic compounds ,biology.protein ,medicine ,Selectivity ,psychological phenomena and processes ,Derivative (chemistry) ,High turnover - Abstract
A metalloporphyrin has been synthesized carrying a beta-cyclodextrin group on tetrafluorophenyl rings at the four meso positions of the porphyrin. It performs the selective hydroxylation of an androstanediol derivative with complete positional selectivity and 187 turnovers.
- Published
- 1998
24. Corrigendum to 'A tetra(ethylene glycol) derivative of benzothiazole aniline ameliorates dendritic spine density and cognitive function in a mouse model of Alzheimer's disease' [Exp. Neurol. 252 (2014) 105–113]
- Author
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Hyang Sook Hoe, Daniel T.S. Pak, Jerry Yang, Jung Min Song, R. Scott Turner, You Me Sung, Joo Myung Ahn, Amanda M. DiBattista, and Hey Kyoung Lee
- Subjects
chemistry.chemical_compound ,Aniline ,Dendritic spine ,Developmental Neuroscience ,Neurology ,chemistry ,Benzothiazole ,biology ,Polymer chemistry ,Tetra ,biology.organism_classification ,Ethylene glycol ,Derivative (chemistry) - Published
- 2014
25. Ion Channel Activity of Amyloid-beta Peptides in Artificial Bilayer Membranes: a Comparison of Different Preparation Techniques
- Author
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Panchika Prangkio, Michael Mayer, Jerry Yang, Mahealani R. Bautista, and Ricardo Capone
- Subjects
0303 health sciences ,biology ,Chemistry ,Amyloid beta ,P3 peptide ,Synthetic membrane ,Biophysics ,Cell membrane ,03 medical and health sciences ,Amyloid disease ,0302 clinical medicine ,Membrane ,medicine.anatomical_structure ,Biochemistry ,biology.protein ,medicine ,Lipid bilayer ,030217 neurology & neurosurgery ,Ion channel ,030304 developmental biology - Abstract
Alzheimer's disease (AD), an ultimately fatal neurodegenerative disorder, is characterized by the presence of plaques containing fibrillar aggregates of amyloid-beta (Aβ) peptides. These peptides, with 39-43 amino acids, especially Aβ(1-40) and Aβ(1-42), are the major components of plaques formed in the brain of patients with AD. Both peptides aggregate rapidly in aqueous solution to form Aβ oligomers as well as Aβ fibrils. An increasing number of evidence suggests that Aβ especially in non fibrillar forms interacts to cell membrane by forming an ion channel or pores through the membrane. One approach to study the mechanism of Aβ is to examine the ion channel activity of Aβ on lipid membrane. A challenge of studying ion channel of Aβ is the difficulty in obtaining the ion channel activity consistently. This study summarizes the 4 different methods of preparation of Aβ(1-40) and Aβ(1-42) which can form ion channel activity on the artificial membrane. We also provide the information on characterization of structural properties, size and kinetics of aggregation of Aβ corresponding to each method of preparation. Our studies may be useful for those who are interested in ion channel approach of Aβ as well as other peptides which share common characteristics in forming ion channel and involve with other amyloid diseases.
- Published
- 2009
- Full Text
- View/download PDF
26. Stimuli-responsive drug delivery systems
- Author
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Jerry Yang
- Subjects
Drug Delivery Systems ,Pharmaceutical Preparations ,Targeted drug delivery ,Stimuli responsive ,Chemistry ,Drug delivery ,Pharmaceutical Science ,Pharmacology ,Drug carrier - Published
- 2012
27. Highly Viscous Coatings from Archaea-Inspired Lipids Improve Single Protein Characterization with Nanopores
- Author
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Geoffray Leriche, Olivia M. Eggenberger, Haiyan Liu, Michael Mayer, Jerry Yang, and Brandon R. Bruhn
- Subjects
Quantitative Biology::Biomolecules ,Physics::Biological Physics ,Chemistry ,Membrane lipids ,Peripheral membrane protein ,Biophysics ,Phospholipid ,Quantitative Biology::Subcellular Processes ,Nanopore ,chemistry.chemical_compound ,Membrane ,Biochemistry ,Monolayer ,lipids (amino acids, peptides, and proteins) ,Lipid bilayer ,Elasticity of cell membranes - Abstract
Despite the importance of proteins, nanopore sensing has so far been mostly focused on single molecule DNA and RNA characterization. One factor that limited experiments with proteins were nonspecific interactions of proteins with the walls of synthetic nanopores. We showed recently, that nanopores with fluid coatings of phospholipid bilayers circumvented this problem. In addition, anchoring proteins to lipid anchors slowed down protein translocation through nanopores and enabled determination of parameters such as the shape, volume, and dipole moment of individual non-spherical proteins. To slow down the translocation time of lipid-anchored proteins further, we have recently formed highly viscous coatings from archaea-inspired lipids. These synthetic lipids are composed of two hydrophilic head groups connected by a long hydrophobic chain; each head group is also attached to an acyl chain that spans half of the membrane thickness. As these lipids contain -in one molecule- the components of a typical lipid bilayer, a single layer is sufficient to form a stable membrane. Monolayers of these new lipids have a two to twenty-fold increased viscosity than typical phospholipid bilayers. The Archaea-inspired lipids discussed here show promise in terms of slowing translocation times and the resulting data made it possible to characterize individual proteins with increased accuracy than coatings from standard phospholipid bilayers.
- Published
- 2014
28. Gramicidin Pores Report the Activity of Membrane-Active Enzymes
- Author
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Alexander D. MacBriar, Michael Mayer, Erik Yusko, Sheereen Majd, and Jerry Yang
- Subjects
Cell signaling ,Lipid Bilayers ,Biophysics ,Phospholipase ,Biochemistry ,Article ,Ion Channels ,Catalysis ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Phosphoinositide phospholipase C ,Phospholipase D ,Lipid bilayer ,chemistry.chemical_classification ,Phospholipase C ,Chemistry ,fungi ,Gramicidin ,Membrane Proteins ,General Chemistry ,Enzyme ,Membrane ,Phospholipases ,Type C Phospholipases ,lipids (amino acids, peptides, and proteins) - Abstract
Phospholipases constitute a ubiquitous class of membrane-active enzymes that play a key role in cellular signaling, proliferation, and membrane trafficking. Aberrant phospholipase activity is implicated in a range of diseases including cancer, inflammation, and myocardial disease. Characterization of these enzymes is therefore important, both for improving the understanding of phospholipase catalysis and for accelerating pharmaceutical and biotechnological applications. This paper describes a novel approach to monitor, in situ and in real-time, the activity of phospholipase D (PLD) and phospholipase C (PLC) on planar lipid bilayers. This method is based on lipase-induced changes in the electrical charge of lipid bilayers and on the concomitant change in ion concentration near lipid membranes. The approach reports these changes in local ion concentration by a measurable change in the single channel ion conductance through pores of the ion channel-forming peptide gramicidin A. This enzyme assay takes advantage of the amplification characteristics of gramicidin pores to sense the activity of picomolar to nanomolar concentrations of membrane-active enzymes without requiring labeled substrates or products. The resulting method proceeds on lipid bilayers without the need for detergents, quantifies enzyme activity on native lipid substrates within minutes, and provides unique access to both leaflets of well-defined lipid bilayers; this method also makes it possible to generate planar lipid bilayers with transverse lipid asymmetry.
- Published
- 2010
29. Developing Nanopores with Fluid Walls for Improved, Single-Molecule Biosensors
- Author
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Michael Mayer, Jiali Li, Jerry Yang, Erik Yusko, Ryan Rollings, Panchika Prangkio, and Alex M. Petti
- Subjects
chemistry.chemical_classification ,Analyte ,Nanopore ,Adsorption ,chemistry ,Biomolecule ,Biophysics ,Molecule ,Nanotechnology ,Lipid bilayer ,Biosensor ,Ion channel - Abstract
Synthetic and biological nanopores can be used for fundamental and applied studies of individual biomolecules in high throughput. By measuring resistive current pulses during the translocation of single molecules through an electrolyte-filled nanopore, this technique can characterize the size, conformation, assembly and activity of hundreds of unlabeled molecules per second. The performance of nanopores fabricated in synthetic materials, however, does not currently match that of biologic ion channels. Major challenges include: (i) achieving precise control of nanopore diameters, (ii) translocation times of molecules that are too fast to be resolved by the best electronics, (iii) a lack of control over the surface chemistry inside synthetic pores, which leads to non-specific adsorption, pore clogging, and unpredictable translocation times, (iv) low frequencies of translocation events at low analyte concentrations and (v) poor specificity of the nanopores for analytes. Inspired by the olfactory sensilla of insect antennae, we demonstrated that coating nanopores with a fluid lipid bilayer addresses all of these challenges while enabling new nanopore-based assays. Coating nanopores with different lipids allows fine control of the surface chemistry and diameter of nanopores. Incorporation of mobile ligands in the lipid bilayer imparts specificity to the nanpore for targeting proteins and enables, for the first time, precise and predictable control of translocation times for targeted proteins based on their net electric charge. Here, we detail how this modification can also be used to determine the affinity of a protein-ligand interaction as well as monitor the kinetics of binding. In addition, the biomimetic lipid surface reduced non-specific adsorption, thereby allowing characterization of Alzheimer's Disease-related amyloid peptides, for which a reliable, biophysical method is lacking.
- Published
- 2012
30. Facile synthesis of β-Cyclodextrin dithiols
- Author
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David Leung and Jerry Yang
- Subjects
Magnetic Resonance Spectroscopy ,Clinical Biochemistry ,Pharmaceutical Science ,Biochemistry ,Chemical synthesis ,Mass Spectrometry ,Potassium carbonate ,chemistry.chemical_compound ,Drug Discovery ,polycyclic compounds ,Organic chemistry ,Molecular Biology ,chemistry.chemical_classification ,Cyclodextrins ,Nucleophilic addition ,Cyclodextrin ,beta-Cyclodextrins ,Organic Chemistry ,technology, industry, and agriculture ,Disulfide bond ,Anisole ,carbohydrates (lipids) ,Sulfonate ,chemistry ,Thiol ,Molecular Medicine ,lipids (amino acids, peptides, and proteins) ,Toluene - Abstract
Nucleophilic addition of 4-methoxy-alpha-toluenethiol to capped cyclodextrins followed by deprotection in TFA affords cyclodextrin dithiols in good yields with no disulfide formation and requires only minimal purification.
- Published
- 2002
31. Nanopores with Fluid Walls
- Author
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Panchika Prangkio, Ryan Rollings, Erik Yusko, Jiali Li, Michael Mayer, Sheereen Majd, Jay M. Johnson, and Jerry Yang
- Subjects
In situ ,Phase transition ,Nanopore ,Viscosity ,Materials science ,Coating ,Biophysics ,engineering ,Nanotechnology ,engineering.material ,Fibril ,Ligand (biochemistry) ,Characterization (materials science) - Abstract
This work introduces the concept of synthetic nanopores with fluid lipid walls and describes the benefit of these pores for single protein translocation experiments. The inspiration for this design comes from lipid-coated nanopores in olfactory sensilla of insect antennae. Multifunctional coatings of fluid lipids enable characterization of single proteins with unprecedented information content and address currently unmet challenges of single protein investigations with nanopores. For instance, translocation events of lipid-anchored proteins reveal the charge, ligand affinity, volume, and molecular shape of single proteins in high throughput. Moreover, translocation of amyloidogenic peptides through a pore with fluid walls makes it possible to characterize a large number of individual Alzheimer's disease-related amyloid-beta fibrils in situ; these fibrils clog conventional nanopores. The choice of lipids in the coating makes it possible to fine-tune the thickness, surface chemistry, functionality, and viscosity of the coating in the pore. These characteristics enable increasing the signal to noise ratio, eliminating non-specific binding, capturing and concentrating specific analytes, increasing translocation times, and time-resolving translocation events completely. Finally, these coatings provide the exquisite sensitivity to monitor thermally-induced conformational changes in bimolecular sheets of lipids and these phase transitions make it possible to actuate the diameters of synthetic nanopore dynamically in situ.
- Published
- 2011
32. Lipid Bilayers in Nanopores to Vary their Diameter, Characterize Amyloid-β Aggregates and Monitor the Activity of Membrane-Active Enzymes
- Author
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Michael Mayer, Ryan Rollings, Jiali Li, Sheereen Majd, Jerry Yang, Erik Yusko, Yazan N. Billeh, and Jay R. Johnson
- Subjects
Nanopore ,Membrane ,Amyloid β ,Coating ,Chemistry ,Bilayer ,Biophysics ,engineering ,Nanometre ,Nanotechnology ,engineering.material ,Lipid bilayer ,Ion - Abstract
This research introduces the concept of coating the surfaces of nanopores with supported lipid bilayers for previously inaccessible nanopore-based assays. Current methods for shrinking nanopores with nanometer precision entail the use of specialized instruments such as focused ion beams or electron beams. Furthermore, altering the surface chemistry of nanopores currently requires multiple chemical steps and typically takes longer than one day. The method presented here modifies the surface chemistry of nanopores within 90 min by deposition of desired lipids with various chemical headgroups. This work also demonstrates the use of lipids with acyl chains of different lengths to shrink the diameter of a nanopore with sub-nanometer precision. Remarkably, the surface of bilayer-coated nanopores is non-fouling and makes it possible to detect aggregates of the "notoriously sticky" peptide, amyloid-β; the same nanopore without a bilayer clogged in every experiment. These non-fouling properties of nanopores coated with a fluid lipid bilayer made it possible to resolve single aggregates of amyloid-β and to characterize their true size distribution. Finally, this research took advantage of bilayer-coated nanopores to monitor the activity of the membrane-active enzyme, phospholipase D. Together the results presented here demonstrate that supported lipid bilayers can be used to alter the size and surface chemistry of nanopores reversibly. Moreover, bilayer-coated nanopores show promise to study membrane-active enzymes, membrane processes, as well as to perform nano-Coulter counter experiments on peptides that aggregate and adhere to surfaces such as amyloid-β.
- Published
- 2010
33. Amyloid-β Ion Channels in Artificial Lipid Bilayers and Neuronal Cells. Resolving a Controversy
- Author
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Michael Mayer, Ricardo Capone, Felipe Garcia Quiroz, Panchika Prangkio, Mahealani R. Bautista, Inderjeet Saluja, Anna M. Sauer, R. Scott Turner, and Jerry Yang
- Subjects
Membrane ,Amyloid ,Voltage-gated ion channel ,Biochemistry ,Chemistry ,Biophysics ,Lipid bilayer ,Resting potential ,Flux (metabolism) ,Ion channel ,Intracellular - Abstract
One of the current hypotheses for the pathology of Alzheimer's disease (AD) proposes that amyloid-beta (Aβ) peptides induce uncontrolled, neurotoxic ion flux across cellular membranes. The resulting inability of neurons to regulate their intracellular concentration of ions, in particular calcium ions, has been associated with cell death and may thus contribute to cognitive impairment typical for AD. The exact biophysical mechanism of this ion flux is subject of an ongoing and unresolved controversy. Two mechanisms are currently debated. One proposed mechanism suggests that Aβ assembles into pore-like structures in lipid membranes, leading to stepwise fluctuations of transmembrane current that is typical for ion channels (ion channel hypothesis). The other proposed mechanism postulates a generalized and gradually increasing ion flux as a result of Aβ-induced thinning of membranes.Here, we resolve this controversy by examining, in detail, the two pivotal protocols for preparing and measuring Aβ induced conductance through planar lipid bilayers and cell membranes. The results clarify that Aβ induces stepwise ion flux across planar lipid bilayers as opposed to a gradual increase in transmembrane current; they show that the previously reported gradual increase in transmembrane current arises from residues of the solvent hexafluoroisopropanol, which is commonly used for the preparation of amyloid samples.We also examined the effect of Aβ samples on cell membranes. We exposed SH-SY5Y neuroblastoma cells and mouse cortical primary neurons to Aβ at resting potential in the presence and absence of typical ion channel blockers. The results provide additional evidence suggesting that Aβ peptides can form ion channels in cellular membranes that are independent from the postulated ability of Aβ to modulate intrinsic cellular ion channels or transporter proteins.
- Published
- 2009
34. Light-gated Ion Channels Based on Gramicidin A
- Author
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Michael Mayer, Mike X. Macrae, and Jerry Yang
- Subjects
Spiropyran ,0303 health sciences ,Biophysics ,Analytical chemistry ,Conductance ,Ion ,03 medical and health sciences ,chemistry.chemical_compound ,Dipole ,0302 clinical medicine ,chemistry ,Functional group ,Gramicidin ,Molecule ,030217 neurology & neurosurgery ,Ion channel ,030304 developmental biology - Abstract
The natural pore-forming peptide gramicidin A has been used for more than twenty years as a platform for sensing. In recent years, the drive has been towards progressively more sensitive detection, approaching the ability to detect single molecules. In an effort to expand the utility of ion channels derived from gramicidin A for sensing applications, we created a neoteric photo-gated gramicidin derivative containing a spiropyran functional group. Upon irradiation with a specific wavelength of light, spiropyrans undergo significant structural rearrangements, including the formation of a quaternary amine, which gives rise to a large (15D) change in dipole moment. We have exploited this unique chemistry by functionalizing the C-terminus of gramicidin with a spiropyran to demonstrate that conductance through these pores can be modulated as a function of the applied wavelength of light. We have also explored the effect of pH on the ion conductance of these light-gated channels. We demonstrate the exquisite responsiveness sensitivity of conductance through these gramicidin pores to various external factors, which may open the door for a number of niche sensing applications for these types of semi-synthetic ion channels.
- Published
- 2009
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