Patents Assigned to Molecular Probes, Inc.
  • Patent number: 5262545
    Abstract: Fluorescent compounds useful in the determination of chloramphenicol acetyltransferase (CAT) enzyme activity are described. The compounds are fluorescent derivatives related in structure to chloramphenicol comprising a base, ##STR1## substituted at one to five aromatic ring positions by substituents, which may be the same or different, that are alkyl-, hydroxy-, alkoxy-, aryl-, halo-, nitro-, amino-, alkylamido-, or arylamido-; and a fluorescent moiety linked to the base at --NH-- by an aliphatic chain of 1-12 atoms other than hydrogen, where such atoms are carbon, nitrogen, oxygen, or sulfur, or combinations thereof. The substrate compounds are acylated in the presence of CAT to produce fluorescent mono- and diacylated products, which are then physically separated from the reaction mixture and quantitated by means of their fluorescence and/or absorbance.
    Type: Grant
    Filed: June 18, 1991
    Date of Patent: November 16, 1993
    Assignee: Molecular Probes, Inc.
    Inventors: Richard P. Haughland, Hee C. Kang, Steven L. Young, Michael H. Melner
  • Patent number: 5248782
    Abstract: This invention describes novel 4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes containing heteroaryl substituents conjugated to the fluorophore and methods for their synthesis. The heteroaryl substituted compounds (heteroaryl dyes) generally have the structure: ##STR1## wherein any or all of the substituents R.sub.1 -R.sub.7, but at least one of such substituents, is a heteroaryl group, including 5- or 6-member rings, singly or fused, containing one or more heteroatoms. The new dyes that have spectral properties that are significantly shifted from those of the parent alkyl-substituted dyes, usually accompanied by an increase in photostability and in some cases by an increase in the extinction coefficient relative to the alkyl-substituted dyes. The general method of synthesis includes formation of pyrromethene salt intermediates followed by cyclization with boron trifluoride in the presence of a base to give heteroaryl-substituted dipyrrometheneboron difluoride dyes.
    Type: Grant
    Filed: December 18, 1990
    Date of Patent: September 28, 1993
    Assignee: Molecular Probes, Inc.
    Inventors: Richard P. Haugland, Hee C. Kang
  • Patent number: 5242805
    Abstract: The claimed invention relates to a substrate for evaluating glycosidic enzymes comprising a resorufin derivative of the general formula: ##STR1## wherein Gly is a carbohydrate bonded to resorufin by a glycosidic linkage; where at least one of substituents R.sub.1, R.sub.2, R.sub.4, R.sub.6, R.sub.8, and R.sub.9 is a lipophilic residue of the formula --L(CH.sub.2).sub.n CH.sub.3, where n is greater than 3 and less than 22, and where L is a methylene --CH.sub.2 --, an amide --NHCO--, a sulfonamide --NHSO.sub.2 --, a carboxamide --CONH--, a carboxylate ester --COO--, a urethane --NHCOO--, a urea --NHCONH--, or a thiourea --NHCSNH--; andwhere the remainder of substituents R.sub.1, R.sub.2, R.sub.4, R.sub.6, R.sub.8, and R.sub.9, which may be the same or different, are hydrogen, halogen, or other lipophilic residues, which may be the same or different, containing from about 1 to about 22 carbon atoms of the formula --L'(CH.sub.2).sub.m CH.sub.3, where m is less than 22, and where L' is a methylene --CH.sub.
    Type: Grant
    Filed: August 23, 1991
    Date of Patent: September 7, 1993
    Assignee: Molecular Probes, Inc.
    Inventors: John J. Naleway, Yu-zhong Zhang, Richard P. Haugland
  • Patent number: 5227487
    Abstract: Novel fluorescent dyes based on the rhodol structure are provided. The new reagents contain functional groups capable of forming a stable fluorescent product with functional groups typically found in biomolecules or polymers including amines, phenols, thiols, acids, aldehydes and ketones. Reactive groups in the rhodol dyes include activated esters, isothiocyanates, amines, hydrazines, halides, acids, azides, maleimides, aldehydes, alcohols, acrylamides and haloacetamides. The products are detected by their absorbance or fluorescence properties. The spectral properties of the fluorescent dyes are sufficiently similar in wavelengths and intensity to fluorescein or rhodamine derivatives as to permit use of the same equipment. The dyes, however, show less spectral sensitivity to pH in the physiological range than does fluorescein, have higher solubility in non-polar solvents and have improved photostability and quantum yields.
    Type: Grant
    Filed: April 16, 1990
    Date of Patent: July 13, 1993
    Assignee: Molecular Probes, Inc.
    Inventors: Richard P. Haugland, James E. Whitaker
  • Patent number: 5208148
    Abstract: The claimed invention relates to a substrate for evaluating glycosidic enzymes comprising a fluorescein derivative of the general formula: ##STR1## wherein GlyX is a carbohydrate bonded to fluorescein by a glycosidic linkage;Y, which may be the same as GlyX or different, is an alkyl ether, an ester, or a glycosidically linked carbohydrate;R is a lipophilic residue containing from 1 to 21 carbon atoms; andL links the R residue to fluorescein.A preferred embodiment of the invention is a non-fluorescent substrate specifically hydrolyzable by a glycosidase inside a cell to yield, after greater than about 2 minutes, a fluorescent detection product excitable at between about 460 nm and 550 nm and with fluorescence observable at an emission wavelength longer than the excitation wavelength, which fluorescent detection product is retained inside a viable cell more than about 2 hours at greater than about 15.degree. C. and which is non-toxic to the cell.
    Type: Grant
    Filed: December 7, 1990
    Date of Patent: May 4, 1993
    Assignee: Molecular Probes, Inc.
    Inventors: Richard P. Haugland, John J. Naleway, Yu-zhong Zhang
  • Patent number: 5187288
    Abstract: This invention relates to ethenyl-substituted derivatives of dipyrrometheneboron difluoride dyes that have an absorption maximum at wavelengths longer than about 525 nm, and are electrically neutral, highly photostable and, in most cases, highly fluorescent with relatively narrow absorption and emission spectra. The ethenyl-substituted dyes generally have the structure: ##STR1## wherein at least one of the fluorophore substituents R.sub.1 -R.sub.7, is an ethenyl group of the formula --CX.sub.m .dbd.CY.sub.m --Z.sub.m, where m is any combination of locations 1, 2, 3, 4, 5, 6, and 7 corresponding to the location of parent fluorophore substituents R.sub.1-7. The initial ethenyl substituents X.sub.m, Y.sub.m, and Z.sub.m, which may be the same or different, are halogen, alkyl (containing 1-10 carbon atoms), cyano, ester, amide, ethenyl or polyethenyl, aryl or heteroaryl.
    Type: Grant
    Filed: May 22, 1991
    Date of Patent: February 16, 1993
    Assignee: Molecular Probes, Inc.
    Inventors: Hee C. Kang, Richard P. Haugland
  • Patent number: 5132432
    Abstract: The invention relates to novel fluorescent dyes based on the following pyrenyloxy sulfonic acid structure: ##STR1## wherein at least one of R.sub.1, R.sub.2, R.sub.3, and R.sub.4 is --OCH.sub.2 C(O)OCH.sub.3, --OCH.sub.2 CON(O)H, --OCH.sub.2 CON.sub.3, --OCH.sub.2 CONHNH.sub.2, ##STR2## or --CH.sub.2 CONH(CH.sub.2).sub.n NH.sub.2 where n is an integer from 1 to 10; at least one of R.sub.1, R.sub.2, R.sub.3, and R.sub.4 is sulfonic acid or alkali salts of sulfonic acid; and all other of R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are hydrogen or a hydroxyl group. The new reagents contain functional groups typically found in biomolecules or polymers. The spectral properties of the fluorescent dyes are sufficiently different in wavelengths and intensity from fluorescein as to permit simultaneous use of both dyes with minimum interference.
    Type: Grant
    Filed: September 22, 1989
    Date of Patent: July 21, 1992
    Assignee: Molecular Probes, Inc.
    Inventors: Richard P. Haugland, James E. Whitaker
  • Patent number: 4945171
    Abstract: Synthesis and applications of fluorescent dyes which are derivatives of benzo[c]xanthenes is described. The dyes exhibit pH dependent absorption and fluorescence spectra with pKas near the normal physiological range. Unlike fluorescein, the dyes exhibit emission of different characteristic wavelengths dependent on the pH of the medium. This permits several methods of measuring the pH of the medium in contact with the indicator including measuring two emissions with one excitation, selectively exiting the acid and base forms independently and measuring their emission at either single or dual wavelengths, or measuring the characteristic pH dependent absorption or fluorescence excitation spectral. Methods are presented for making the indicators permeant to cell membranes for the measurement of intracellular pH.
    Type: Grant
    Filed: August 10, 1987
    Date of Patent: July 31, 1990
    Assignee: Molecular Probes, Inc.
    Inventors: Richard P. Haugland, James Whitaker
  • Patent number: 4774339
    Abstract: Novel fluorescent dyes based on the dipyrrometheneboron difluoride structure are provided. The new reagents contain functional groups capable of forming a stable fluorescent product with functional groups typically found in biomolecules or polymers including amines, phenols, thiols, acids, aldehydes and ketones. Reactive groups in the dipyrrometheneboron difluoride dyes include activated esters, isocyanates, amines, hydrazines, sulfonyl halides, acids, aldehydes, alcohols and haloacetamides. The products are detected by their absorbance or fluorescence properties. The spectral properties of the fluorescent dyes are sufficiently similar in wavelengths and intensity to fluorescein as to permit use of the same euqipment. The dyes, however, have narrower spectral bandwidths than fluorescein, do not show appreciable sensitivity to pH, have higher solubility in non-polar solvents and have improved photostability.
    Type: Grant
    Filed: August 10, 1987
    Date of Patent: September 27, 1988
    Assignee: Molecular Probes, Inc.
    Inventors: Richard P. Haugland, Hee C. Kang