Boehringer Mannheim Gmbh

Roche Diagnostics Gmbh

Roche Molecular Systems, Inc.

Boehringer Mannhiem Gmbh

Klaus Muhlegger

Herbert Von Der Eltz

Hans-Georg Batz

Gunter Weimann

Hans-Joachim Guder

Sibylle Berner

Heinz-Hartmut Seliger

Dieter Heindl

Hans-Peter Josel

Rupert Herrmann

Erasmus Huber

Frank Seela

Albert Roder

Klaus Beaucamp

Gregor Sagner

Axel Schmidt

Jutta Arden-Jacob

Walter Schneider

Michael Nelboeck-Hochstetter

Hans-Georg Ihlenfeldt

Bruno Zink

Zigmunt Kasimierczuk

Karl Heinz Drexhage

Volker Leitenberger

Jorg Frantzeskos

The invention concerns compounds of the general formula (I) in which the residues Rto Rhave the meanings given in the application as well as methods for their preparation. The compounds are in particular suitable as substrates for RNA or DNA polymerases and can thus be incorporated into RNA or DNA oligonucleotides and are especially suitable for labelling and detecting nucleic acids or for DNA sequencing. 

Heterocyclic compounds and their use in the detection of nucleic acids

The invention concerns stable aqueous solutions containing one or several nucleoside triphosphates wherein the respective solution has a pH value of more than 7.5 and contains no additional substances with a stabilizing effect. The nucleoside triphosphate solutions are used in particular for DNA synthesizing reactions such as e.g. RT-PCR, cycle sequencing, random priming and nick translation. One of the most important applications of such solutions containing deoxy-nucleoside triphosphates (d-NTP) is their use in the polymerase chain reaction (PCR).

Stabilized aqueous nucleoside triphosphate solutions

The invention concerns rhodamine derivatives of the general formulae

Rhodamine derivatives and the use thereof

2'-Deoxyisoguanosine, isosteric analogues and isoguanosine derivatives of formulae I-V, processes for their production via compounds of the general formulae a or b and reaction with aroyl isocyanates or from compounds of the general formulae VI-IX by photochemical irradiation. A further production process is the conversion of deoxyguanosines or guanosines by means of persilylation, reaction with ammonia and deamination in the 2 position. The compounds are suitable as pharmaceutical agents with antiviral efficacy.

2-deoxy-isoguanosines isoteric analogues and isoguanosine containing

The subject matter of the invention is a modified phosphoramidite process for the synthesis of nucleotide sequences. By use of a modified nucleoside phosphoramidite it is possible to produce nucleotide sequences which have a modified phosphate residue.

Modified phosphoramidite process for the production of modified nucleic

The present invention provides digoxigenin derivatives of the formula: ##STR1## wherein n is a whole number of from 1 to 4 and Z is a carboxyl group or a functional derivative derived therefrom. The present invention also provides digoxigenin conjugates of the general formula: ##STR2## wherein the carrier is an immunogenic carrier material, a nucleic acid or a labelled immunocomponent of a labelled digoxigenin immunoconjugate for use in an immunoassay, m is a number from 1 to the number of coupling positions available on the carrier and Y is the group formed by the reaction of the carboxyl function Z of the digoxigenin derivative of general formula (I) with the reacting position of the carrier material. Also described are uses of these conjugates as nucleic acid probes, immunogens, and in immunoassay.

Digoxigenin derivatives and use thereof

Reagents for the determination of hydrolase comprises compounds of the formula ##STR1## wherein Z is an organic or inorganic acid residue or a sugar residue, A is an organic or inorganic acid residue, and B is an organic acid residue. Each of R.sup.2 and R.sup.5, is hydrogen, halogen or lower alkyl. Each of R.sup.1, R.sup.3, R.sup.4 and R.sup.6, is hydrogen, halogen, cyano, lower alkyl, lower alkoxy, carboxyl, lower alkoxycarbonyl, carboxy lower alkyl or lower alkoxycarbonyl lower alkyl, or carboxamido groups optical substituted once or twice, or a radical of the formula

Hydrolase substrates

Reagents for the determination of hydrolase comprises compounds of the formula ##STR1## wherein Z is an organic or inorganic acid residue or a sugar residue, A is an organic or inorganic acid residue, and B is an organic acid residue. Each of R.sup.2 and R.sup.5, is hydrogen, halogen or lower alkyl. Each of R.sup.1, R.sup.3, R.sup.4 and R.sup.6, is hydrogen, halogen, cyano, lower alkyl, lower alkoxy, carboxyl, lower alkoxycarbonyl, carboxy lower alkyl or lower alkoxycarbonyl lower alkyl, or carboxamido groups optional substituted once or twice, or a radical of the formula

New hydrolase substrates

The present invention provides phosphates of resorufin derivatives of the general formulae: ##STR1## wherein R.sup.2 and R.sup.5, which can be the same or different, are hydrogen or halogen atoms or lower alkyl radicals, R.sup.1, R.sup.3, R.sup.4 and R.sup.6, which can be the same or different, are hydrogen or halogen atoms, cyano or carboxy groups or lower alkyl, lower alkoxy, lower alkoxycarbonyl, carboxy lower alkyl or lower alkoxycarbonyl lower alkyl radicals or carboxamide groups which are optionally mono- or disubstituted or radicals of the general formula --COO--(CH.sub.2 CH.sub.2 O).sub.n --R.sup.7, R.sup.7 being a hydrogen atom or a lower alkyl radical and n being a whole number of from 1 to 4, and wherein R.sup.6 can additionally also be a sulphonyl or nitro group, Y is a nitrogen atom or an N.fwdarw.O group and M and M', which can be the same or different, are hydrogen atoms or alkali metal, alkaline earth metal or ammonium ions. The present invention also provides processes for the preparation of these compounds and diagnostic agents containing them for the detection of phosphatases.

Phosphates of resorufin derivatives and compositions thereof for the

Crystalline salts of .beta.-nicotinamide-adenine-dinucleotide (.beta.-NAD), particularly alkali metal salts thereof are prepared in good yield and high quality to provide an analytically useful .beta.-NAD form.

Crystalline metal salts of .beta.-nicotinamide-adenine-dinucleotide

NADP-dependent dehydrogenases are separated and purified by subjecting mixtures containing it to affinity chromatography using as the affinity chromatography material a nucleotide with a phosphate group in the 2'- or 3'-position, bound to a solid carrier.

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Polling, Germany

Klaus Muhlegger