Abstract: The present invention relates to the preparation and use of therapeutic compounds for the treatment of diseases at specific subcellular target areas such as specific cellular organelles. In particular, the therapeutic compounds of the invention are specific for modifying enzyme activity within targeted organelles or structures of cells and tissues. Subcellular organelles and structures that may be specifically targeted by compounds of the present invention include lysosomes, autophagasomes, the endoplasmic reticulum, the Golgi complex, peroxisomes, the nucleus, membranes and the mitochondria.

Abstract: This invention relates to substrates and methods for the visualization of intracellular organelles, such as the lysosome, peroxiosome, nucleus, Endoplasmic Reticulum and Golgi Apparatus, based upon organelle enzyme activity. Such compounds represent a novel combination of chemically distinct enzyme substrates with targeting and detection substrates which are activated by enzyme activity inside target organelles to produce a detectable signal. The organelle targeted enzyme substrates of this invention are designed to provide high fluorescence at lower pH values found in some organelles and can be used for monitoring enzyme activity inside cells at very low concentrations.

Abstract: The present invention relates to the preparation and use of therapeutic compounds for the treatment of diseases at specific subcellular target areas such as specific cellular organelles. In particular, the therapeutic compounds of the invention are specific for modifying enzyme activity within targeted organelles or structures of cells and tissues. Subcellular organelles and structures that may be specifically targeted by compounds of the present invention include lysosomes, autophagasomes, the endoplasmic reticulum, the Golgi complex, peroxisomes, the nucleus, membranes and the mitochondria.

Abstract: This invention relates to substrates and methods for the visualization of intracellular organelles, such as the lysosome, peroxiosome, nucleus, Endoplasmic Reticulum and Golgi Apparatus, based upon organelle enzyme activity. Such compounds represent a novel combination of chemically distinct enzyme substrates with targeting and detection substrates which are activated by enzyme activity inside target organelles to produce a detectable signal. The organelle targeted enzyme substrates of this invention are designed to provide high fluorescence at lower pH values found in some organelles and can be used for monitoring enzyme activity inside cells at very low concentrations.

Abstract: 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.

Abstract: The present invention relates to the preparation and use of therapeutic compounds for the treatment of diseases at specific subcellular target areas such as specific cellular organelles. In particular, the therapeutic compounds of the invention are specific for modifying enzyme activity within targeted organelles or structures of cells and tissues. Subcellular organelles and structures that may be specifically targeted by compounds of the present invention include lysosomes, autophagasomes, the endoplasmic reticulum, the Golgi complex, peroxisomes, the nucleus, membranes and the mitochondria.

Abstract: The present invention provides systems and methods for production of activatable diazo-derivatives for use in labeling nucleotides. Labeling nucleotides is accomplished by contacting a stable hydrazide derivative of a detectable moiety with an activating polymer reagent which is used to directly label the nucleotide sample. Labeling occurs on the phosphate backbone of the nucleotide which does not perturb hybridization of the labeled nucleotide with its anti-sense strand. Since the method involves direct labeling, all types of nucleotides can be labeled without prior amplification or alteration.

Abstract: Novel pro-drugs and methods for their use to alter the growth and biological characteristics of living cells, tissues, or whole organisms are described. Such cells may include animal cells, plant cells and bacterial cells. The methods allow for selective activation of the pro-drugs at or near transformant host cells expressing a gene for an enzyme that activates the pro-drugs. Pro-drugs according to a preferred embodiment of the invention are conjugates of a bioactive compound and a chemical group that is capable of being cleaved from the bioactive compound by action of an enzyme. Methods according to this invention include, (a) introducing into targeted cells a gene encoding an enzyme and (b) administering a pro-drug, wherein the enzyme releases the pro-drug from conjugation. In a preferred embodiment of the invention, the gene encoding the enzyme is a marker gene.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: A codon optimized and stabilized luciferase gene based upon the sequence of the natural luciferase gene isolated from Luciola cruciata (Japanese firefly) 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.

Abstract: A codon optimized and stabilized luciferase gene based upon the sequence of the natural luciferase gene isolated from Luciola cruciata (Japanese firefly) 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.

Abstract: A codon optimized and stabilized luciferase gene based upon the sequence of the natural luciferase gene isolated from Luciola cruciata (Japanese firefly) 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.

Abstract: Novel pro-drugs and methods for their use to alter the growth and biological characteristics of living cells, tissues, or whole organisms are described. The methods allow for selective activation of the pro-drugs at or near transformant host cells expressing a gene for an enzyme that activates the pro-drugs. Pro-drugs according to a preferred embodiment of the invention are conjugates of a bioactive compound and a chemical group that is capable of being cleaved from the bioactive compound by action of an enzyme. Methods according to this invention include, (a) introducing into targeted cells a gene encoding an enzyme and (b) administering a pro-drug, wherein the enzyme releases the pro-drug from conjugation. In a preferred embodiment of the invention, the gene encoding the enzyme is a marker gene.

Abstract: Novel pro-drugs and methods for their use to alter the growth and biological characteristics of living cells, tissues, or whole organisms are described. The methods allow for selective activation of the pro-drugs at or near transformant host cells expressing a gene for an enzyme that activates the pro-drugs. Pro-drugs according to a preferred embodiment of the invention are conjugates of a bioactive compound and a chemical group that is capable of being cleaved from the bioactive compound by action of an enzyme. Methods according to this invention include, (a) introducing into targeted cells a gene encoding an enzyme and (b) administering a pro-drug, wherein the enzyme releases the pro-drug from conjugation. In a preferred embodiment of the invention, the gene encoding the enzyme is a marker gene.