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WO2000047548A1 - Composes de liaison proteinique ameliores - Google Patents

Composes de liaison proteinique ameliores Download PDF

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Publication number
WO2000047548A1
WO2000047548A1 PCT/AU2000/000075 AU0000075W WO0047548A1 WO 2000047548 A1 WO2000047548 A1 WO 2000047548A1 AU 0000075 W AU0000075 W AU 0000075W WO 0047548 A1 WO0047548 A1 WO 0047548A1
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Prior art keywords
compound according
group
membrane
substitute sheet
moiety
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PCT/AU2000/000075
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English (en)
Inventor
Ping Yin
Christopher John Burns
Matthew Peter Wilkinson
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Australian Membrane And Biotechnology Research Institute
The University Of Sydney
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Application filed by Australian Membrane And Biotechnology Research Institute, The University Of Sydney filed Critical Australian Membrane And Biotechnology Research Institute
Priority to EP00904701A priority Critical patent/EP1150942A4/fr
Priority to JP2000598469A priority patent/JP2002536428A/ja
Priority to AU26485/00A priority patent/AU2648500A/en
Priority to CA002341348A priority patent/CA2341348A1/fr
Publication of WO2000047548A1 publication Critical patent/WO2000047548A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C217/28—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C237/12—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/16—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
    • C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
    • C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
    • C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
    • C07C2603/18—Fluorenes; Hydrogenated fluorenes

Definitions

  • the present invention relates to novel binding compounds, in particular protein binding compounds.
  • novel compounds are particularly useful for binding proteins to surface including membranes.
  • the present invention provides biosensors incorporating these protein binding compounds.
  • the present invention also extends to intermediate compounds for use in the synthesis of the binding compounds of the present invention.
  • Ternaiy metal complexes are well known in the literature (1) and can be described as the coordination of two discrete metal chelating groups to a metal.
  • the metals normally observed in ternary complexes are Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ .
  • Typical metal coordinating groups are nitrilotriacetic acid (NT A), iminodiacetic acid (IDA), catechols, and aromatic nitrogen containing heterocycles such as imidazole.
  • Ternary complexes have been characterised by numerous methods including potentiometric calculations (2) and X-ray crystallography (3). These studies have allowed the stability of simple ternary complexes to be determined with the average stability constant (Ka) being 10 3 -lu 4 M '1 (4).
  • IMAC Immobilised Metal Affinity Chromatography
  • the stability of the ternary complex i.e. the interaction between the metal chelate the metal and the protein, is often too weak for proteins to be immobilised for a sufficiently long period for observation and study.
  • the metal chelates employed interact in a non-specific manner with other non-tagged proteins.
  • the ternary complexes can be broken down in the presence of certain interferents at concentrations not unknown in certain assay systems.
  • the present inventors have developed compounds with improved characteristics to those compounds already disclosed in the literature. These compounds possess a plurality of metal-chelating groups covalently linked. The compounds can be used to attach proteins to materials and surfaces.
  • the present invention consists in a compound, the compound having the general Formula I
  • Y is a branching moiety and Z represents a polydentate ligand chelating agent that coordinates a metal ion; and n is an integer of at least 2, preferably from 2 to 9.
  • Z may be a polydentate ligand that coordinates a metal ion such as Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ .
  • the donor atoms of Z may be ⁇ - donor atoms or ⁇ - donor atoms.
  • the donor atoms may be selected from N, O, S, P and Si.
  • the donor atoms are N.
  • Z may be bidentate, tridentate (for example IDA) or quadradentate (for example NTA).
  • Z is other than a cyclic or polycyclic.
  • Z is a quadradentate ligand such as NTA.
  • Y provides at least three moieties for covalent attachment directly, or indirectly through an optional linking group, to Z.
  • the backbone of branching group Y may be a residue of a compound, an oligomer or a polymer.
  • the linking group has a linear backbone.
  • the present invention provides a compound of formula II
  • X may be hydrophilic, hydrophobic or have both hydrophobic and hydrophilic regions.
  • X may be or include a substituted or unsubstituted alkyl, optionally interrupted by one or more heteroatoms (eg 0, N, S or combinations of two or more thereof), for example oligoethylene glycol or other oligoalkylene
  • X may be, or include, a lipid.
  • the lipid may be a membrane spanning lipid (MSL).
  • MSL membrane spanning lipid
  • X includes an hydrophilic region, for example polyalkylene oligomer, and an hydrophobic region, for example a lipid, wherein X is attached to Y via an hydrophobic region optionally via a spacer.
  • the present invention provides a compound of Formula III
  • X, Y, Z and n are as described above and W is a group that allows for attachment to other molecules, or attachment to surfaces, or insertion into membrane(s).
  • W is a group which allows for attachment to other molecules including polymers such as Sepharose (such as an amine functional group, a carboxylic acid functional group, an alcohol functional group, a halide functional group) or attachment to surfaces (such as a thiol or disulfide for attachment to gold or other coinage metal surfaces, or such as a silane derivative for attachment to oxide surfaces) or insertion into membranes (such as a lipid group, or a membrane soluble protein, such as gramicidin). W may also be a group which enables non-covalent attachment such as biotin to streptavidin.
  • polymers such as Sepharose (such as an amine functional group, a carboxylic acid functional group, an alcohol functional group, a halide functional group) or attachment to surfaces (such as a thiol or disulfide for attachment to gold or other coinage metal surfaces, or such as a silane derivative for attachment to oxide surfaces) or insertion into membranes (such as a lipid group, or a membrane soluble
  • Y is a branching moiety that provides a plurality of moieties for covalent attachment of Z and a single moiety for covalent attachment of X.
  • Non-limiting illustrative examples of Y include: amino-polyols such as TRIS, bis-homotris
  • amino acids such as 3,5-diaminobenzoic acid, 5-aminoisophthalic acid,
  • Substitute Sheet peptides which possess multiple free acid and/or amine moieties, for example
  • Y is a branching moiety where there is a plurality of moieties for covalent attachment of Z and X.
  • Non-limiting illustrative examples of Y include:
  • polyamines such as spermjdine, spermine, pentaethylenehexamine
  • polyacids such as tartaric acid, trimesic acid, citric acid, Kemp's triacid
  • polyhydroxylated materials such as sugars
  • dendrons such as the commercially available “Starburst” compounds
  • nucleophiles such as halides, tosylates
  • groups to which nucleophiles readily add such as , ⁇ -unsaturated ketones
  • the compounds of the present invention may have a wide range of uses. In particular they are useful for the attachment of proteins and other biological macromolecules to surfaces. As will be understood this is a requirement of a multitude of sensing devices and assays.
  • Biosensors are well known in the art and are described in PCT/AU93/00620, PCT/AU96/00482, PCT/AU95/00763,
  • biosensors there is provided a membrane which includes ionophores and receptors. Binding of an analyte to the receptors causes a detectable change in the conductance or impedance of the membrane.
  • receptors directed against the analyte of interest are attached to the ionophore and to the membrane.
  • the receptors are proteins such as antibodies or antigen binding fragments thereof such as Fab'. It is believed that the binding compounds of the present invention will be useful in the attachment of such receptors to the ionophores and membrane of the biosensors.
  • FIG. 1 Binding of 6His.Rubisco to Jl.triNTA chip. 100, 200 and 400 nM binding curves shown (bottom to top). Binding curves are the responses from Fc2 (control, -Ni 2+ ) subtracted from Fcl.
  • Binding of 6His.CD40 to Jl.triNTA chip 100, 200, 400, 600 and 800 nM binding curves shown (bottom to top). Binding curves are the responses from Fc2 (control, -Ni 2+ ) subtracted from Fcl.
  • Binding of 6HIS.CD40 to triNTA has a 12 fold higher affinity than to NTA. This is mainly as a result of a 10-fold higher on rate (k .
  • the off rate (k for the NTA binding is likely to be exaggerated.
  • N6-carbobenzyloxy-L-lysine,2-tTimethylsilylethanol, l-(3-dimethylaminopropyl)-3- ethylcarbodiiuiide hydrochloride (EDC), dicyclohexylcarbodiimide (DCC), N- hydroxysuccinamide (NHS) and 6-aminocaproic acid (X) were obtained from Sigma- Aldrich chemical company.
  • XXBoc was prepared by reacting XBoc NHS ester (itself obtained by protection of the amino group of X with BocON under standard conditions, and subsequent coupling with NHS using DCC) with X.
  • Dichloromethane was distilled over P 2 O 5 immediately prior to use.
  • Substitute Sheet 25 ml was added dropwise to the reaction mixture over 2 h. The solution was allowed to warm to room temperature and stirred at room temperature overnight. The reaction mixture was heated at 50°C for 2 h, then allowed to cool to room temperature. An aqueous solution of HC1 (IM, 40 ml) was added dropwise to the reaction mixture, and the resulting white precipitate was filtered and washed with HC1 (0.1M, 20 ml) and distilled water (2x20 ml). The resulting white solid was dried under high vacuum for several days to afford Z-LysNTA as a white solid (2.68 g, 95% yield).
  • Electrospray M/S m/z 397 (100%) (M+H + ), 398 (21%), 353 (30%), 792 (15%).
  • ZLysNTA.TMSE 3 was synthesised using a procedure outlined by Gao et al. 2
  • Substitute Sheet stirred at room temperature overnight. Distilled water (50 ml) was added to the reaction mixture, and the organic layer was separated. The aqueous layer was extracted with dichloromethane (2x50 ml), and the organic extracts were combined and dried over anhydrous sodium carbonate. The mixture was filtered and all volatiles were removed under reduced pressure to afford a colourless oil. Purification by column chromatography on flash silica using a solvent gradient from dichloromethane to 5% methanol in dichloromethane afforded ZLysNTA.TMSE 3 as a colourless oil (0.75 g, 86%).
  • Electrospray M/S m/z 719.4 (100%) (M+Na + )
  • Substitute Sheet Rul 2 R ⁇ U multiplets 3.26-3.16 (10H, overlapping multiplets), 3.07 (IH, triplet), 1.85-1.30 (24H, overlapping multiplets, 12 x -CH 2 ), 0.97 (18H, overlapping multiplets, 9 x -CH 2 Si-), 0.05 (27H, s, 3 x -Si(CH 3 ) 3 ), 0.04 (54H, s, 6 x -Si(CH 3 ) 3 ) ppm.
  • Electrospray M/S m/z 2054.3 (100%) (M+Na + ), 1038.8 (20%), 613.3 (36%)
  • Electrospray M/S m/z 1151.4 (100%) (M+Na + ), 1129.2 (88%) (M+H + ), 1130.3 (56%) (M+2H + ), 1152.4 (53%) (M+Na + +H + ), 1165.3 (53%), 1143.3 (52%), 755.5 (50%), 907.2 (41%), 393.2 (26%).
  • Electrospray M/S m/z 2019.8 (35%), ( +Na + ), 1997.8 (100%) (M + ).
  • NTA TMSE 9 34 mg,0.0179 mmol was triturated with toluene, evaporated and dried under high vacuum.
  • Trifluoroacetic acid (1 ml) was added and stirred under nitrogen atmosphere 0-5° C for 2 hours, then at room temperature overnight. The trifluoroacetic acid was evaporated and the residue was triturated with toluene again, evaporated and dried to afford t ⁇ NTA (20 mg, 100%).
  • Gramicidin (75 mg, 0.0398 mmol) was dissolved in pyridine (0.5 ml) and succinic anhydride (20 mg, 0.200 mmol) was added. The mixture was stirred under nitrogen atmosphere at 50° C for 20 hours and evaporated. The crude product was passed down a sephadex LH-20 column in methanol, the eluate was evaporated and purified on a flash silica column using dichloromethane/methanol/water/acetic acid (400:50:4:1). The product was further purified by centrifuging with water. The water was decanted and the product was dried under high vacuum to give gramicidin succinate (53 mg, 67%).
  • Gramicidin succinate (21 mg, 0.0105 mmol), N-hydroxysuccinamide (12 mg, 0.1042 mmol) and 4-dimethylamino pyridine (2.5 mg, 0.0204 mmol) were combined with distilled tetrahydrofuran (10 ml). With stirring under nitrogen dicyclohexylcarbodiimide (22 mg, 0.1066 mmol) was added. The mixture was heated to reflux for one hour. The mixture was evaporated and passed down a sephadex LH- 20 column in methanol. Appropriate fractions were evaporated and dried to give gramicidin succinate NHS (22 mg, 100%).
  • Lysine tri NTA (20 mg, 0.0201 mmol) was dissolved in methanol (1 ml) and triethylamine (2 drops) was added to neutralise. Then gramicidin succinate NHS (15
  • Gramicidin lysine 2XBOC (12 mg,0.0052 mmol) was triturated with toluene, evaporated and dried under high vacuum. Trifluoroacetic acid (1 ml) was added, evaporated under nitrogen and dried. Again toluene was added, evaporated and dried under high vacuum. The crude amine was dissolved in pyridine (0.5 ml) and reacted with succinic anhydride (2.6 mg, 0.0259mmol). The reaction mixture was stirred at room temperature for 20 hours. Pyridine was removed under high vacuum and the residue was passed down the sephadex LH-20 column in methanol. The product was further purified on a flash silica column eluted with methanol to give gAlysine 2X Succinate (10 mg, 83%).
  • Substitute Sheet 0.0363mmol was added. The mixture was refluxed under nitrogen for 1 hour. The mixture was evaporated and purified on a sephadex LH-20 column in methanol. Appropriate fractions were evaporated and added to lysine tri NTA (8.5 mg, 0.0085 mmol). The mixture was stirred at room temperature for 18 hours. The reaction mixture was evaporated and purified on sephadex LH-20 in methanol (X2). Gramicidin lysine 2Xtri NTA (2.6 mg, 19%) was obtained (due to low solubility some compound was lost).
  • Electrospray M/S m/z 1173.9 (100%), 2146.4 (25%) (M+Na + ).
  • Trifluoroacetic acid (2 ml) was added to Biotin.triNTA.TMSE 9 (19 mg, 9 umol) at 0°C.
  • the reaction mixture was stirred at 0°C for 3 hour, after which time all volatiles were removed under reduced pressure.
  • Electrospray M/S m/z 1221.5 (100%) (M+H + ), 1243.4 (33%) (M+Na + ).
  • Electrospray M/S m/z 1486.6 (100%) (M+H + ), 1508.8 (62%) (M+Na + ).
  • the reaction mixture was added with chloroform (50 mL) and then washed successively with 40 mL portions of water (x2), 3% potassium carbonate (x2), water (x2), 5% HC1 (x2) and water (x2). (NB.
  • the phase separation was extremely tedious due to emulsion formation at each of the successive wash. In order to improve the process an addition of methanol was necessary.
  • the organic phases were combined and dried over sodium sulphate. The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography. [Eluant; dichloromethane: acetone: methanol: ammonium hydroxide (8:5:5:3)] 122 mg of colourless waxy material was obtained.
  • Substitute Sheet ( Rule 26) RO/AU 2X-Boc (420mg) was treated with TFA (5mL) for 20 mins under nitrogen atmosphere. TFA was removed under reduduced pressure and dried under high vacuum. This residue was then dissolved in 9% aqueous sodium carbonate solution (6mL) and the solution cooled to 0°C. Fmoc-NMS ester (purchased from CALBIOCHEM) (420mg) dissolved in DMF(3mL) was added into the above stirring solution at 0°C and stirred at RT for 30 mins. Water (lOOmL) was added and aqueous solution extracted with ethyl acetate (2x50mL) and organic extracts were discarded. Aqueous layer acidified with concentrated hydrochloric acid (2-3mL) and cooled in an ice bath during which a precipitate appeared. This precipitate was filtered and dried to give white powder (210mg).
  • the Fmoc protected material (200mg) was dissolved in a solution of piperidine:DMF (20:80) stirred at room temperature for 10 minutes. DMF removed under reduced pressure and the crude material was purified by column chromatography (methanol :aqueous ammonia: DCm 10:2:88). Pure product was isolated as a colorless semi-solid (148mg).
  • the NHS ester of this material was prepared by reaction of the acid (50mg) with NHS (8mg) in the presence of DCC (15mg) and DMAP (2.6mg) in CH 2 C1 2 (3ml) for 4h and purified by passage through a Sephadex LH-20 column eluting with methanol.
  • SPR Surface Plasmon Resonance
  • This Jl.triNTA chip was docked into a BIAcore 2000 machine and the pumps flushed and experiments performed using HBS/EDTA running buffer (50 mM HEPES, 300 mM NaCl. 50 ⁇ M EDTA, pH 8 0) at a flow rate of 40 ⁇ l/min at 21 °C Flow cell 2 (Fc2) was used as the test cell relative to the control Flow cell 1 (Fcl)
  • running buffer containing 500 ⁇ M N ⁇ Cl 2 was injected through Fc2 only, which was then washed with running buffer for 5 min
  • the protein of interest 100-600 nM
  • Substitute Sheet 17 Liley, M., Keller, T.A., Duschl, C, Vogel, H., Langmuir, 1997, 13, 4190.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Peptides Or Proteins (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

L'invention concerne de nouveaux composés de liaison protéinique représentés par la formule (III): W-X-Y-(Z)n dans laquelle Y représente une fraction ramifiée, Z représente un agent de chélation d'un ligand polydente qui coordonne un ion métallique, X représente une fraction d'espacement, n est un nombre entier d'au moins 2 et W représente un groupe permettant la fixation à d'autres molécules, à des surfaces ou l'introduction dans des membranes.
PCT/AU2000/000075 1999-02-08 2000-02-08 Composes de liaison proteinique ameliores WO2000047548A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP00904701A EP1150942A4 (fr) 1999-02-08 2000-02-08 Composes de liaison proteinique ameliores
JP2000598469A JP2002536428A (ja) 1999-02-08 2000-02-08 タンパク質結合のための改良化化合物
AU26485/00A AU2648500A (en) 1999-02-08 2000-02-08 Improved compounds for protein binding
CA002341348A CA2341348A1 (fr) 1999-02-08 2000-02-08 Composes de liaison proteinique ameliores

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AUPP8563A AUPP856399A0 (en) 1999-02-08 1999-02-08 Improved compounds for protein binding
AUPP8563 1999-02-08

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WO2000047548A1 true WO2000047548A1 (fr) 2000-08-17

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CA (1) CA2341348A1 (fr)
WO (1) WO2000047548A1 (fr)

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WO2003091689A3 (fr) * 2002-03-28 2004-12-23 Rutgers The State Of Universit Sondes a chelates a deux metaux de transition
WO2005003383A1 (fr) * 2003-07-08 2005-01-13 Tacnia Pty Ltd Ameliorations des puces de detection
WO2005029075A1 (fr) * 2003-09-17 2005-03-31 Rutgers, The State University Of New Jersey Sondes de deux chelates metalliques de transition
WO2006013042A3 (fr) * 2004-08-05 2006-06-01 In Johann Wolfgang Goethe Uni Chelateurs polyvalents pour la modification et l'organisation de molecules cibles
US7371585B2 (en) 2003-12-31 2008-05-13 Genencor International, Inc. Membranes incorporating recognition moieties
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WO2010084996A1 (fr) * 2009-01-22 2010-07-29 Fujifilm Corporation Substrat, procédé de fabrication de ce substrat, et dispositif d'extraction
WO2011101445A1 (fr) * 2010-02-18 2011-08-25 Johann Wolfgang Goethe-Universität Frankfurt am Main Composés chélateurs multivalents (mch) à haute affinité et leur utilisation pour l'analyse structurelle et fonctionnelle de molécules cibles
US8137733B2 (en) 2007-11-22 2012-03-20 Fujifilm Corporation Process for producing a carrier
US20130142864A1 (en) * 2003-08-21 2013-06-06 Lipotek Pty Ltd. In vivo targeting of dendritic cells
US8557194B2 (en) 2007-07-13 2013-10-15 Fujifilm Corporation Carrier, process for producing same, bioreactor, and chip for surface plasmon resonance analysis
WO2013160453A3 (fr) * 2012-04-26 2014-02-20 Iba Gmbh Molécule adaptatrice capable de munir une protéine de fusion portant une étiquette d'affinité oligohistidine d'une autre étiquette d'affinité et ses procédés d'utilisation
US20170045522A1 (en) * 2014-04-29 2017-02-16 Yeda Research And Development Co. Ltd. Fluorescent molecular sensor for targeting changes in protein surfaces, and methods of use thereof
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US20210156867A1 (en) * 2014-04-29 2021-05-27 Yeda Research And Development Co. Ltd. Quinoline based cyanine dye turn-on fluorescent probes and methods of use thereof

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CN116970027A (zh) * 2020-11-04 2023-10-31 中国药科大学 哑铃型两亲性肽类树形分子、合成及其作为药物递送系统的应用

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990005303A1 (fr) * 1988-11-10 1990-05-17 Pharmacia Ab Surfaces de captage capables d'interactions biomoleculaires selectives, a utiliser dans des systemes de biocapteurs
AU3608995A (en) * 1994-09-23 1996-04-09 Boehringer Ingelheim International Gmbh Process of investigating the interaction between biomolecules by means of surface plasmon resonance
WO1996031557A1 (fr) * 1995-04-07 1996-10-10 Mogens Havsteen Jacobsen Procede d'immobilisation photochimique de ligands a l'aide de quinones
US5580527A (en) * 1992-05-18 1996-12-03 Moltech Corporation Polymeric luminophores for sensing of oxygen
US5620850A (en) * 1994-09-26 1997-04-15 President And Fellows Of Harvard College Molecular recognition at surfaces derivatized with self-assembled monolayers
WO1998000435A2 (fr) * 1996-07-03 1998-01-08 President And Fellows Of Harvard College Segment de liaison pour oligonucleotide et techniques comprenant des oligonucleotides immobilises et lies
US5834224A (en) * 1994-08-24 1998-11-10 Boehringer Mannhein Gmbh Electrochemical sensor containing an enzyme linked to binding molecules bound to a noble metal surface
US5846814A (en) * 1996-02-27 1998-12-08 Bayer Aktiengesllschaft Solid-supported membrane biosensors

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3158635A (en) * 1959-03-18 1964-11-24 Stauffer Chemical Co Bis-adduction products and methods of preparing same
US3700671A (en) * 1967-05-15 1972-10-24 Monacelli Walter J Chelating compositions
GB8610551D0 (en) * 1986-04-30 1986-06-04 Hoffmann La Roche Polypeptide & protein derivatives
US5342604A (en) * 1988-10-31 1994-08-30 The Dow Chemical Company Complexes possessing ortho ligating functionality
US5096946A (en) * 1989-08-18 1992-03-17 Rainer Norman B Polymer product for the selective absorption of dissolved ions
US5800802A (en) * 1989-10-11 1998-09-01 Subramanian; Ramaswamy Chelator IDAC-2
DE19505960A1 (de) * 1995-02-21 1996-08-22 Deutsches Krebsforsch Konjugat zur individuellen Dosierung von Arzneimitteln
DE19518421A1 (de) * 1995-05-19 1996-11-21 Basf Ag Oligomere der Asparaginsäure
GB9813776D0 (en) * 1998-06-25 1998-08-26 Smithkline Beecham Plc Novel compounds

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990005303A1 (fr) * 1988-11-10 1990-05-17 Pharmacia Ab Surfaces de captage capables d'interactions biomoleculaires selectives, a utiliser dans des systemes de biocapteurs
US5580527A (en) * 1992-05-18 1996-12-03 Moltech Corporation Polymeric luminophores for sensing of oxygen
US5834224A (en) * 1994-08-24 1998-11-10 Boehringer Mannhein Gmbh Electrochemical sensor containing an enzyme linked to binding molecules bound to a noble metal surface
AU3608995A (en) * 1994-09-23 1996-04-09 Boehringer Ingelheim International Gmbh Process of investigating the interaction between biomolecules by means of surface plasmon resonance
US5620850A (en) * 1994-09-26 1997-04-15 President And Fellows Of Harvard College Molecular recognition at surfaces derivatized with self-assembled monolayers
WO1996031557A1 (fr) * 1995-04-07 1996-10-10 Mogens Havsteen Jacobsen Procede d'immobilisation photochimique de ligands a l'aide de quinones
US5846814A (en) * 1996-02-27 1998-12-08 Bayer Aktiengesllschaft Solid-supported membrane biosensors
WO1998000435A2 (fr) * 1996-07-03 1998-01-08 President And Fellows Of Harvard College Segment de liaison pour oligonucleotide et techniques comprenant des oligonucleotides immobilises et lies

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
KELLER ET AL.: "Reversible oriented immobilisation of histidine-tagged proteins on gold surfaces using a chelator thioalkane", SUPRAMOLECULAR SCIENCE,, vol. 2, DATE 1995, no. 3-4, 1996, pages 155 - 160 *
See also references of EP1150942A4 *
VO-DINH ET AL.: "Detection of cadmium ion using the fluorescence probwe indo-1 reference to 'EGTA' and Fura 2'", ANALYTICA CHIMICA ACTA,, vol. 295, no. 1-2, 1994, pages 67 - 72 *

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003091689A3 (fr) * 2002-03-28 2004-12-23 Rutgers The State Of Universit Sondes a chelates a deux metaux de transition
JP2005530166A (ja) * 2002-06-20 2005-10-06 プロテオメ ファクトリー アーゲー サンプル中の１種または２種以上のタンパク質を特異的に同定および定量化するための方法および試薬
WO2004001420A3 (fr) * 2002-06-20 2004-03-04 Proteome Factory Ag Procede et reactif destines a l'identification specifique et a la quantification d'au moins une proteine dans un echantillon
AU2003242721B2 (en) * 2002-06-20 2009-12-03 Humboldt-Universitat Zu Berlin Method and reagent for specifically identifying and quantifying one or more proteins in a sample
AU2004254295B2 (en) * 2003-07-08 2010-05-27 Tacnia Pty Ltd Improvements in sensor chips
WO2005003383A1 (fr) * 2003-07-08 2005-01-13 Tacnia Pty Ltd Ameliorations des puces de detection
US7759114B2 (en) 2003-07-08 2010-07-20 Tacnia Pty Ltd Sensor chips
US20130142864A1 (en) * 2003-08-21 2013-06-06 Lipotek Pty Ltd. In vivo targeting of dendritic cells
WO2005029075A1 (fr) * 2003-09-17 2005-03-31 Rutgers, The State University Of New Jersey Sondes de deux chelates metalliques de transition
US7371585B2 (en) 2003-12-31 2008-05-13 Genencor International, Inc. Membranes incorporating recognition moieties
US9606114B2 (en) 2004-08-05 2017-03-28 Johann Wolfgang Goethe-Universitat Frankfurt Am Main Multivalent chelators containing a scaffold structure for modifying and organizing of target molecules
WO2006013042A3 (fr) * 2004-08-05 2006-06-01 In Johann Wolfgang Goethe Uni Chelateurs polyvalents pour la modification et l'organisation de molecules cibles
DE102004038134B4 (de) * 2004-08-05 2013-07-25 Johann Wolfgang Goethe-Universität Frankfurt am Main Multivalente Chelatoren zum Modifizieren und Organisieren von Zielmolekülen, Verfahren zu ihrer Herstellung sowie ihre Verwendung
US8557194B2 (en) 2007-07-13 2013-10-15 Fujifilm Corporation Carrier, process for producing same, bioreactor, and chip for surface plasmon resonance analysis
US8137733B2 (en) 2007-11-22 2012-03-20 Fujifilm Corporation Process for producing a carrier
WO2010084996A1 (fr) * 2009-01-22 2010-07-29 Fujifilm Corporation Substrat, procédé de fabrication de ce substrat, et dispositif d'extraction
WO2011101445A1 (fr) * 2010-02-18 2011-08-25 Johann Wolfgang Goethe-Universität Frankfurt am Main Composés chélateurs multivalents (mch) à haute affinité et leur utilisation pour l'analyse structurelle et fonctionnelle de molécules cibles
WO2013160453A3 (fr) * 2012-04-26 2014-02-20 Iba Gmbh Molécule adaptatrice capable de munir une protéine de fusion portant une étiquette d'affinité oligohistidine d'une autre étiquette d'affinité et ses procédés d'utilisation
US20170045522A1 (en) * 2014-04-29 2017-02-16 Yeda Research And Development Co. Ltd. Fluorescent molecular sensor for targeting changes in protein surfaces, and methods of use thereof
US10557852B2 (en) * 2014-04-29 2020-02-11 Yeda Research And Development Co. Ltd. Fluorescent molecular sensor for targeting changes in protein surfaces, and methods of use thereof
US20200256857A1 (en) * 2014-04-29 2020-08-13 Yeda Research And Development Co. Ltd. Universal histidine-tag binding compounds and methods of use thereof as fluorescent probes and sensors
US20210156867A1 (en) * 2014-04-29 2021-05-27 Yeda Research And Development Co. Ltd. Quinoline based cyanine dye turn-on fluorescent probes and methods of use thereof
US11639929B2 (en) * 2014-04-29 2023-05-02 Yeda Research And Development Co. Ltd. Universal histidine-tag binding compounds and methods of use thereof as fluorescent probes and sensors

Also Published As

Publication number Publication date
EP1150942A4 (fr) 2003-02-12
CN1345301A (zh) 2002-04-17
JP2002536428A (ja) 2002-10-29
AUPP856399A0 (en) 1999-03-04
EP1150942A1 (fr) 2001-11-07
CA2341348A1 (fr) 2000-08-17

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