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EUGENE, OR, United States

Carroll C.N.,University of Oregon | Carroll C.N.,Oregon Nanoscience and Microtechnologies Institute | Naleway J.J.,Oregon Nanoscience and Microtechnologies Institute | Naleway J.J.,Marker Gene Technologies | And 4 more authors.
Chemical Society Reviews

This critical review will focus on the application of shape-persistent receptors for anions that derive their rigidity and optoelectronic properties from the inclusion of arylethynyl linkages. It will highlight a few of the design strategies involved in engineering selective and sensitive fluorescent probes and how arylacetylenes can offer a design pathway to some of the more desirable properties of a selective sensor. Additionally, knowledge gained in the study of these receptors in organic media often leads to improved receptor design and the production of chromogenic and fluorogenic probes capable of detecting specific substrates among the multitude of ions present in biological systems. In this ocean of potential targets exists a large number of geometrically distinct anions, which present their own problems to the design of receptors with complementary binding for each preferred coordination geometry. Our interest in targeting charged substrates, specifically how previous work on receptors for cations or neutral guests can be adapted to anions, will be addressed. Additionally, we will focus on the design and development of supramolecular arylethynyl systems, their shape-persistence and fluorogenic or chromogenic optoelectronic responses to complexation. We will also examine briefly how the "chemistry in the cuvet" translates into biological media (125 references). © 2010 The Royal Society of Chemistry. Source

Marker Gene Technologies | Date: 2013-05-14

The present invention relates to the visualization of acidic organelles based upon organelle enzyme activity. The organelle substrates of the invention are specific for enzyme activity of the organelle and label these organelles, such as lysosomes, rendering them visible and easily observed. Substrates of the present invention include substrates that produce a fluorescent signal. The fluorogenic acidic organelle enzyme substrates of this invention are designed to provide high fluorescence at low pH values and are derivatized to permit membrane permeation through both outer and organelle membranes of intact cells and can be used for staining cells at very low concentrations. They can be used for monitoring enzyme activity in cells at very low concentrations and are not toxic to living cells or tissues.

Marker Gene Technologies | Date: 2012-12-04

A codon optimized and stabilized luciferase gene and a novel recombinant DNA characterized by incorporating this new gene coding for a novel luciferase into a vector DNA for improved activities in mammalian cells, are disclosed. This new luciferase exhibits long-wavelength light emission, as well as improved thermostability and higher expression levels in mammalian cell systems, compared to native luciferase. Assays using this new enzyme for measuring various biological metabolic functions are described.

Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 99.96K | Year: 2008

This Small Business Innovation Research (SBIR) Phase I research project aims to develop novel nucleic acid labeling reagents that can be used in living cells to monitor gene expression. Instead of relying on labeling the molecules using fluorescently labeled bases, the proposed approach relies on adding the label to the terminal phosphates. This would have great advantage over existing methods and would be a welcome addition to the tools of molecular analysis. Current detection of the changes in gene expression relies on the labeling of nucleic acids with fluorescent labels, which sometimes interferes with hybridization. Thus development of a technology that allows labeling of the nucleic acids in such a way so as to not affect the molecules? hybridization parameters would be a significant advance. Moreover, such a technology would make quantitiation of the hybridization event easier as the fluorescence intensity of the probe molecules would not be sequence dependent. In addition, the obviation of the need for enzyme incorporation and amplification methods would reduce the time and cost associated with the labeling of probes.

Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 224.59K | Year: 2015

DESCRIPTION provided by applicant This Small Business Innovation Research Phase I project aims to develop new targeted pharmacological chaperones capable of modulating enzyme degradation in the Golgi apparatus and Endoplasmic Reticulum ER of living cells and tissues If successful the proposed research will provide breakthroughs needed to advance the discovery of promising new therapies and modulating drugs for neurodegenerative disorders including lysosomal storage diseases Alzheimerandapos s disease AD amyotrophic lateral sclerosis ALS Parkinsonandapos s disease PD myeloid leukemia glioblastoma Type diabetes Lowe syndrome and allied degenerative diseases and medical conditions involving protein misfolding In Phase I of this project Marker Gene Technologies Inc will establish the feasibility of the technology by preparing new targeted pharmacological chaperones demonstrating improved loading and localized accumulation in the Golgi and ER and demonstrating efficacy for increasing lysosomal enzyme activity in living cells that are of disease origin in comparison to those from normal controls In Phase II these and additional new targeted drug conjugates will be evaluated in vitro and in vivo for their ability to affect specific and localized induction of tese enzymes in living cells as well as alleviate unwanted protein degradation or improve protein trafficking in a cell or tissue specific manner using a variety of delivery methods These new pharmacological chaperones and the resulting targeting systems will provide innovative methods to modulate Golgi and ER organelle function and thereby screen for the influence of secondary drug or protein administration affect intracellular trafficking of proteins or improve transport or secretion of proteins making them useful analytical tools for drug discovery and basic research in a variety of significant medical applications Our very preliminary results indicate the proposed methods have the potential to increase intracellular loading and targeting of pharmacological chaperones in human cell lines from patients with Gaucher disease thereby providing a new tool to the arsenal of available therapeutics for clinical treatment of neurodegenerative disorders PUBLIC HEALTH RELEVANCE The success of this project opens up enormous commercial possibilities in the fields of medical intervention in a variety of neurodegenerative diseases such lysosomal storage diseases Alzheimerandapos s disease AD amyotrophic lateral sclerosis ALS Parkinsonandapos s disease PD myeloid leukemia glioblastoma Type diabetes Lowe syndrome and allied medical conditions as well as in the screening of new proteins and drugs in cell culture systems for efficacy in modulating intracellular enzyme activity in these diseases The development of new general and organelle specific targeting strategies will find use in potential treatment of organelle specific viral and bacterial diseases such as Cholera Chlamydia or malarial infection The developed products will also be useful in non mammalian cells systems that exhibit defective protein folding and ER Golgi accumulation or degradation including plant yeast and bacterial species and will lead to commercial and licensable products in these areas

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