Carnegie Mellon University

Ge Healthcare UK Limited

Ge Healthcare Limited

Amersham International Plc

Amersham Biosciences UK Limited

Nigel Bosworth

Ratnakar B Mujumdar

Richard Martin West

Klaes Golman

Alan L Hamilton

Jan Wolber

Peter Knox

Colin David Bell

Neil Cook

John Hewer Howse

Mike Looker

Martyn N Birch

Brian Scott

Jan Jenrik Ardenkjaer-Larsen

Malcolm J Hatcher

Albie Santos

David Martin James

The invention is concerned with Nuclear Magnetic Resonance (NMR) spectroscopy and Magnetic Resonance Imaging (MRI), particularly NMR spectroscopy. It provides hyperpolarization methods offering enhanced sensitivity of detection over conventional NMR for studying the fate of a test compound in a biological system. The methods are particularly suitable for studying metabolism and toxicity of drugs. The resulting NMR sensitivity increase is advantageous in two key aspects of NMR detection: test compounds can be detected at lower concentrations and substantial time saving can be achieved in cases where extensive averaging is conventionally employed to increase the signal to noise ratio of the corresponding NMR spectra. The methods can be used for studios that were not practical or not possible using conventional NMR.

Method for investigating the fate of a test compound or the stateof a biological system by means of NMR of hyperpolarised NMR active nuclei

Disclosed are cyanine dyes that are useful for labelling and detecting biological and other materials. The dyes are of formula (I): in which groups Rand Rare attached to the Zring structure and groups Rand Rare attached to the Zring structure, and n=1, 2 or 3; Zand Zindependently represent the carbon atoms necessary to complete a one ring, or two-fused ring aromatic system; at least one of groups R, R, R, R, R, Rand Ris the group -E-F where E is a single bond or a spacer group and F is a target bonding group; one or more of groups R, R, Rand Rare independently selected from the group &#x2014;(CH)&#x2014;W, where W is sulphonic acid or phosphonic acid and k is an integer from 1 to 10. The dyes may be used in fluorescence labelling applications, where the presence of one and preferably multiple water solubilizing groups attached to the 3-position of the indolinium ring reduces dye-dye interactions, and hence dye-dye quenching, particularly where multiple dye molecules are attached to components such as nucleic acids, oligonucleotides, proteins and antibodies.

Cyanine dye labelling reagents

Disclosed are cyanine dyes that are useful for labeling and detecting biological and other materials. The dyes are of formula (I) in which groups Rand Rare attached to the Zring structure and groups Rand Rare attached to the Zring structure, and n=1, 2 or 3; Zand Zindependently represent the carbon atoms necessary to complete a one ring, or two-fused ring aromatic system; at least one of groups R, R, R, R, R, Rand Ris the group -E-F where E is a single bond or a spacer group and F is a target bonding group; one or more of groups R, R, Rand Rare independently selected from the group &#x2014;(CH)&#x2014;W, where W is sulphonic acid or phosphonic acid and k is an integer from 1 to 10. The dyes may be used in fluorescence labeling applications, where the presence of one and preferably multiple water solubilising groups attached to the 3-position of the indolinium ring reduces dye-dye interactions, and hence dye-dye quenching, particularly where multiple dye molecules are attached to components such as nucleic acids, oligonucleotides, proteins and antibodies. 

Disclosed is a non-fluorescent cyanine dye that may be used as an acceptor in fluorescence energy transfer assays involving the detection of binding and/or cleavage events in reactions involving biological molecules, and assay methods utilising such dyes. The non-fluorescent cyanine dye is a compound of formula (I), wherein the linker group Q contains at least one double bond and forms a conjugated system with the rings containing X and Y; groups R , R , R and R are attached to the rings containing X and Y, or optionally, are attached to atoms of the Z and Z ring structures; Z and Z each represent a bond or the atoms necessary to complete one or two fused aromatic rings each ring having five or six atoms, selected from carbon atoms and, optionally, no more than two oxygen, nitrogen and sulphur atoms; at least one of groups R , R , R , R , R , R and R is a target bonding group; any remaining groups R , R , R , R and R groups are independently selected from the group consisting of hydrogen, C -C alkyl, OR , COOR , nitro, amino, acylamino, quaternary ammonium, phosphate sulphonate and sulphate, where R is selected from H and C -C alkyl; any remaining R and R are selected from C -C alkyl which may be unsubstituted or substituted with phenyl, the phenyl being optionally substituted by up to two substituents selected from carboxyl, sulphonate and nitro groups; characterised in that at least one of the groups R , R , R , R , R , R and R comprises a substituent which reduces the fluorescence emission of said dye such that it is essentially non-fluorescent.

Energy transfer assay method and reagent

Novel compounds obtainable by reacting together an imido-reagent such as diphenylphosphonimido-triphenylphosphorane), or a phosphine oxide such as p-tolyldiphenylphosphine oxide, with a chelate of a transition or lanthanide or actinide metal, such as tris(dibenzoylmethide)europium III, have the property of fluorescing in UV radiation. The invention includes solid polymer bodies containing such compounds, or chelates of transition or lanthanide or actinide metals generally, the bodies having the property of emitting light or infra-red radiation when subjected to a flux of ultra-violet or ionising radiation by virtue of internally generated, e.g. by tritium ionising radiation. The body is preferably of polystyrene formed by polymerising the monomer in the presence of the compound or metal chelate.

Fluorescent compounds

Growing community of inventors

Cardiff, United Kingdom

Nigel Bosworth