公开(公告)号：EP1276749A1

公开(公告)日：2003-01-22

申请号：EP01929464.4

申请日：2001-03-26

申请人： Forschungsverbund Berlin e.V. ,  Forschungszentrum Jülich GmbH

发明人： HAGEN, Volker ,  KAUPP, Ulrich, Benjamin ,  BENDIG, Jürgen ,  WIESNER, Burghard

IPC分类号： C07H19/20 ,  A61K31/7076 ,  A61K31/708

CPC分类号： C07H19/20

摘要： The invention relates to novel, photo-labile cumarinylmethyl esters of cyclic nucleotides of general formula (I): axial isomer (Ia), equatorial isomer (Ib); wherein R1 represents hydrogen, bromine or p-chlorophenylthio, R4 represents 7-carboxymethoxy, 6,7-, 5,7- or 7,8- bis(car-boxymethoxy), 7-C¿1?-C3-alkoxycarbonylmethoxy, 6,7-bis(C1-C3-alkoxycarbonylmethoxy), 5,7-bis(C1-C3-alkoxycarbonylmethoxy) or 7,8-bis(C1-C3-alkoxy-carbonylmethoxy), R?2¿ represents -NH¿2? and R?3¿ is hydrogen (adenine radical) or R2 denotes -OH and R3 denotes -NH¿2? (guanine radical). The inventive compounds are biologically inactive and have a high solvolysis resistance, exhibiting high solubility in aqueous buffer solutions, high photocleavage and quick release kinetics.

公开(公告)号：EP0786086B1

公开(公告)日：1999-12-08

申请号：EP95933318.8

申请日：1995-09-30

申请人： FORSCHUNGSZENTRUM JÜLICH GMBH

发明人： THUST, Marion ,  SCHÖNING, Michael, Josef ,  VETTER, Joachim ,  KAUPP, Ulrich, Benjamin ,  KORDOS, Peter ,  LÜTH, Hans

IPC分类号： G01N33/543 ,  C12N11/14 ,  C07K17/14 ,  G01N33/552

CPC分类号： C12N11/14 ,  C12N9/86 ,  G01N33/54353 ,  G01N33/551 ,  G01N33/552 ,  G01N2415/00

摘要： In order to immobilise bio-material, e.g. enzymes, micro-organisms, cells, organelles, etc., on a substrate with a Si3N4 surface with bonding-active NHx groups, use is made of a hetero-functional cross-linking agent with a bio-material coupling function on the one hand and a NHx-reactive group on the other. The immobilisation substrate preferably takes the form of a 10-1000 mm thick Si3N4 layer which is separated from SiH4/NH3 by CVD and coated with bonding-active NHx groups by hydrolysing surface cleaning, especially with dilute acid. Advantageously, a hetero-bifunctional cross-linking agent is first caused to react with an NH2-reactive aldehyde, ester, halide, epoxide, imine or isocyanate group and, after the removal of unbonded superfluous cross-linking agent, coupled to the biomaterial by means of the bio-reactive group.

公开(公告)号：EP0784791A1

公开(公告)日：1997-07-23

申请号：EP95933316.0

申请日：1995-09-30

申请人： FORSCHUNGSZENTRUM JÜLICH GMBH

发明人： THUST, Marion ,  SCHÖNING, Michael, Josef ,  VETTER, Joachim ,  KAUPP, Ulrich, Benjamin ,  KORDOS, Peter ,  LÜTH, Hans

IPC分类号： C12M1 ,  C12Q1 ,  G01N27 ,  G01N33

CPC分类号： G01N33/54373 ,  C12Q1/001

摘要： The successful bonding of bioactive material, especially enzymes, to the signal-active surface of a biosensor can be achieved by means of a heterobifunctional crosslinking agent having a group A reactive for the signal-active surface, e.g. a group reacting with -OH, -SH or -NHx, and a photoactivatable, biomaterial-reactive group B. Known groups B are, in particular, azidophenyl and azidosalicylic groups. Crosslinking agents containing such groups B on the one hand and succinimide ester groups on the other are commercially available and hence particularly attractive. The signal-active surface can be especially a Si3N4 surface with reactive NHx groups, as can be obtained from the gas phase by SiH4/NH3 reaction, especially on a fresh SiO2 surface, and has been freed from oxides especially by treatment with dilute hydrofluoric acid.

公开(公告)号：EP0853628B1

公开(公告)日：2002-10-02

申请号：EP96927617.9

申请日：1996-07-29

申请人： Forschungsverbund Berlin e.V. ,  Forschungszentrum Jülich GmbH

发明人： HAGEN, Volker ,  KAUPP, Ulrich, Benjamin

IPC分类号： C07H19/20

CPC分类号： A61K41/0042 ,  C07H19/20

摘要： The invention concerns photolabile 8-substituted guanosine-3',5'-cyclomonophosphate esters and 8-substituted adenosine-3',5'-cyclomonophosphate esters of formula (I) and methods of preparing these compounds by reacting the appropriate 8-substituted cyclic nucleotides with substituted diazoalkanes or substituted bromoalkanes or by substitution reactions at the 8-position of the appropriate 8-bromoguanosine-3',5'-cyclomonophosphate esters or 8-bromoadenosine-3',5'-cyclomonophosphate esters. The invention also concerns the use of such compounds. The compounds are suitable for use in the investigation of processes dependent on cyclic nucleotides. Fields of application are biological, biochemical, biophysical, physiological and medical research (formula (I)).

公开(公告)号：EP0853628A1

公开(公告)日：1998-07-22

申请号：EP96927617.0

申请日：1996-07-29

申请人： Forschungsverbund Berlin e.V. ,  FORSCHUNGSZENTRUM JÜLICH GMBH

发明人： HAGEN, Volker ,  KAUPP, Ulrich, Benjamin

IPC分类号： A61K31 ,  A61K41 ,  A61P43 ,  C07H19

CPC分类号： A61K41/0042 ,  C07H19/20

摘要： The invention concerns photolabile 8-substituted guanosine-3',5'-cyclomonophosphate esters and 8-substituted adenosine-3',5'-cyclomonophosphate esters of formula (I) and methods of preparing these compounds by reacting the appropriate 8-substituted cyclic nucleotides with substituted diazoalkanes or substituted bromoalkanes or by substitution reactions at the 8-position of the appropriate 8-bromoguanosine-3',5'-cyclomonophosphate esters or 8-bromoadenosine-3',5'-cyclomonophosphate esters. The invention also concerns the use of such compounds. The compounds are suitable for use in the investigation of processes dependent on cyclic nucleotides. Fields of application are biological, biochemical, biophysical, physiological and medical research (formula (I)).

公开(公告)号：EP1276749B1

公开(公告)日：2005-08-24

申请号：EP01929464.4

申请日：2001-03-26

申请人： Forschungsverbund Berlin e.V. ,  FORSCHUNGSZENTRUM JÜLICH GMBH

发明人： HAGEN, Volker ,  KAUPP, Ulrich, Benjamin ,  BENDIG, Jürgen ,  WIESNER, Burghard

IPC分类号： C07H19/20 ,  A61K31/7076 ,  A61K31/708

CPC分类号： C07H19/20

摘要： The invention relates to novel, photo-labile cumarinylmethyl esters of cyclic nucleotides of general formula (I): axial isomer (Ia), equatorial isomer (Ib); wherein R represents hydrogen, bromine or p-chlorophenylthio, R represents 7-carboxymethoxy, 6,7-, 5,7- or 7,8- bis(car-boxymethoxy), 7-C1-C3-alkoxycarbonylmethoxy, 6,7-bis(C1-C3-alkoxycarbonylmethoxy), 5,7-bis(C1-C3-alkoxycarbonylmethoxy) or 7,8-bis(C1-C3-alkoxy-carbonylmethoxy), R represents -NH2 and R is hydrogen (adenine radical) or R denotes -OH and R denotes -NH2 (guanine radical). The inventive compounds are biologically inactive and have a high solvolysis resistance, exhibiting high solubility in aqueous buffer solutions, high photocleavage and quick release kinetics.

公开(公告)号：EP0784791B1

公开(公告)日：2001-11-21

申请号：EP95933316.2

申请日：1995-09-30

申请人： FORSCHUNGSZENTRUM JÜLICH GMBH

发明人： THUST, Marion ,  SCHÖNING, Michael, Josef ,  VETTER, Joachim ,  KAUPP, Ulrich, Benjamin ,  KORDOS, Peter ,  LÜTH, Hans

IPC分类号： G01N33/543 ,  G01N27/414 ,  C12Q1/00

CPC分类号： G01N33/54373 ,  C12Q1/001

摘要： The successful bonding of bioactive material, especially enzymes, to the signal-active surface of a biosensor can be achieved by means of a heterobifunctional crosslinking agent having a group A reactive for the signal-active surface, e.g. a group reacting with -OH, -SH or -NHx, and a photoactivatable, biomaterial-reactive group B. Known groups B are, in particular, azidophenyl and azidosalicylic groups. Crosslinking agents containing such groups B on the one hand and succinimide ester groups on the other are commercially available and hence particularly attractive. The signal-active surface can be especially a Si3N4 surface with reactive NHx groups, as can be obtained from the gas phase by SiH4/NH3 reaction, especially on a fresh SiO2 surface, and has been freed from oxides especially by treatment with dilute hydrofluoric acid.

公开(公告)号：EP0786086A1

公开(公告)日：1997-07-30

申请号：EP95933318.0

申请日：1995-09-30

申请人： FORSCHUNGSZENTRUM JÜLICH GMBH

发明人： THUST, Marion ,  SCHÖNING, Michael, Josef ,  VETTER, Joachim ,  KAUPP, Ulrich, Benjamin ,  KORDOS, Peter ,  LÜTH, Hans

IPC分类号： G01N33 ,  C07K17 ,  C12N9 ,  C12N11

CPC分类号： C12N11/14 ,  C12N9/86 ,  G01N33/54353 ,  G01N33/551 ,  G01N33/552 ,  G01N2415/00

摘要： In order to immobilise bio-material, e.g. enzymes, micro-organisms, cells, organelles, etc., on a substrate with a Si3N4 surface with bonding-active NHx groups, use is made of a hetero-functional cross-linking agent with a bio-material coupling function on the one hand and a NHx-reactive group on the other. The immobilisation substrate preferably takes the form of a 10-1000 mm thick Si3N4 layer which is separated from SiH4/NH3 by CVD and coated with bonding-active NHx groups by hydrolysing surface cleaning, especially with dilute acid. Advantageously, a hetero-bifunctional cross-linking agent is first caused to react with an NH2-reactive aldehyde, ester, halide, epoxide, imine or isocyanate group and, after the removal of unbonded superfluous cross-linking agent, coupled to the biomaterial by means of the bio-reactive group.