EP0454778A4 - Molecules with antibody combining sites that exhibit stereospecific catalysis - Google Patents
Molecules with antibody combining sites that exhibit stereospecific catalysisInfo
- Publication number
- EP0454778A4 EP0454778A4 EP19900902870 EP90902870A EP0454778A4 EP 0454778 A4 EP0454778 A4 EP 0454778A4 EP 19900902870 EP19900902870 EP 19900902870 EP 90902870 A EP90902870 A EP 90902870A EP 0454778 A4 EP0454778 A4 EP 0454778A4
- Authority
- EP
- European Patent Office
- Prior art keywords
- ligand
- reactant ligand
- atom
- receptor
- ester
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
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- 238000000034 method Methods 0.000 claims description 18
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Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0002—Antibodies with enzymatic activity, e.g. abzymes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/10—Cells modified by introduction of foreign genetic material
- C12N5/12—Fused cells, e.g. hybridomas
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4071—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4087—Esters with arylalkanols
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/42—Halides thereof
- C07F9/425—Acid or estermonohalides thereof, e.g. RP(=X)(YR)(Hal) (X, Y = O, S; R = H, or hydrocarbon group)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
Definitions
- immunologieal binding aay be used to experimentally divert binding interactions to catalytic processes.
- use of an antibody to a haptenic group that resembles the transition state of a given reaction should cause an acceleration in substrate reaction by forcing substrates to resemble the transition state.
- Jencks, W.P. Catalysis in Chemistry and Enzymology, page 288 (McGraw-Hill, New York 1969).
- specific transition state haptens were not suggested, nor were specific reactions suggested in which the concept might be tested.
- an analog-ligand aolecule and/or a reactant ligand aolecule can contain aore than one stereoisomeric center.
- a second, 'third or other such center is located at such a distance from the scissile carbonyl carbon (or phosphorus atom) that it is not bound by a receptor aolecule, it is of no aatter herein.
- any other stereoisomeric center produces additional stereoisomers.
- the number of such isomers is determined by the equation: number » 2 n , where n is the number of stereoisomeric centers.
- the at least one stereoisomeric center can be on either the carboxylic acid or alcohol or amine portions of the ester or amide reactant ligand and analog-ligand. If more than one such center is present in the reactant ligand and analog-ligand molecules, that plurality of stereoisomeric centers can be distributed in any way desired about the scissile carbonyl carbon atom (or central phosphorus atom). Any stereoisomerism provided by the central tetrahedral phosphorus atom is not considered herein.
- hydrolysis of carboxylic acid esters is a simpler example of transacylation that should also be approximated by the phosphonate-containing analog of the transition state.
- the binding of the charged phosphonate group may describe a stabilizing interaction in the transition state that would lead to catalysis. Ester hydrolysis reactions generally proceed at convenient spontaneous rates under ambient conditions that are suitable for antibodies. Therefore, any small rate acceleration can be readily detected.
- the present invention generally relates to monoclonal receptors, that are capable of catalytically hydrolyzing a preselected amide or ester bond of one stereoisomer of a reactant ligand.
- the receptors contain an antibody combining site that binds: (a) to one stereoisomer of a reactant ligand that can form the tetrahedral hydrolytic transition state of a preselected ester or amide bond of the reactant; i.e., contains a preselected carboxylic acid amide or ester bond, and (b) to one stereoisomer of an analog-ligand that is stereochemically analogous to the reactant ligand and has a tetrahedrally bonded phosphorus atom located at the position occupied by the scissile carbonyl group carbon atom of the preselected ester or amide bond of the reactant ligand.
- the tetrahedrally bonded phosphorus atom is bonded directly to:
- a solution was prepared containing 0.0461 g (3.773xl0 ⁇ 4 aoles) of S(-) ⁇ ec-phenethyl alcohol and 0.0525 al of triethylamine (one equivalent) dissolved in CH 2 C1 2 . That solution was stirred at room temperature for one-half hour.
- the above-prepared acid chloride (0.10g; 3.774x10 moles) then was added followed by another equivalent of triethylamine. Addition of the acid chloride caused the solution to turn brown, and additon the amine caused a solid to start precipitating. The reaction mixture was stirred for one-half hour.
- the carrier-hapten conjugate is dissolved or dispersed in an aqueous composition of a physiologically tolerable diluent such as normal saline, PBS, or sterile water to form an inoculum.
- a physiologically tolerable diluent such as normal saline, PBS, or sterile water
- An adjuvant such as complete or incomplete Freund's adjuvant or alum can also be included in the inoculum.
- the inoculum is introduced as by injection into the animal used to raise the antibodies in an amount sufficient to induce antibodies, as is well known.
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Application Number | Priority Date | Filing Date | Title |
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US297798 | 1981-08-31 | ||
US29779889A | 1989-01-17 | 1989-01-17 |
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EP0454778A1 EP0454778A1 (en) | 1991-11-06 |
EP0454778A4 true EP0454778A4 (en) | 1993-10-06 |
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EP19900902870 Withdrawn EP0454778A4 (en) | 1989-01-17 | 1990-01-12 | Molecules with antibody combining sites that exhibit stereospecific catalysis |
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EP (1) | EP0454778A4 (fi) |
JP (1) | JPH04502708A (fi) |
KR (1) | KR910700334A (fi) |
AU (1) | AU650846B2 (fi) |
CA (1) | CA2007816A1 (fi) |
FI (1) | FI95928C (fi) |
GR (1) | GR900100025A (fi) |
IE (1) | IE63274B1 (fi) |
PT (1) | PT92884B (fi) |
WO (1) | WO1990008185A1 (fi) |
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US5229272A (en) * | 1989-04-25 | 1993-07-20 | Igen, Inc. | Catalytic antibody components |
US5236825A (en) * | 1989-01-17 | 1993-08-17 | Scripps Clinic And Research Foundation | Polyvalent metal ion-containing antibody combining site catalysts |
EP1443963B1 (en) * | 2001-10-22 | 2014-05-21 | The Scripps Research Institute | Antibody targeting compounds |
CN110950960B (zh) * | 2019-11-26 | 2021-05-14 | 中国农业大学 | 基于高通量测序和杂合杂交瘤技术的小分子化合物抗体的制备方法 |
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WO1988009380A1 (en) * | 1987-05-28 | 1988-12-01 | Scripps Clinic And Research Foundation | Antibody combining sites that exhibit stereoselective synthase activity, and methods using the same |
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US4659567A (en) * | 1984-09-07 | 1987-04-21 | Scripps Clinic & Research Foundation | Molecules with antibody combining sites that bind to hydrolytic transition states |
US4792446A (en) * | 1986-06-23 | 1988-12-20 | Igen, Inc. | Production of antibody catalysts |
US4963355A (en) * | 1986-06-23 | 1990-10-16 | Igen, Inc. | Production of antibody catalysts |
-
1990
- 1990-01-12 WO PCT/US1990/000269 patent/WO1990008185A1/en not_active Application Discontinuation
- 1990-01-12 JP JP2503094A patent/JPH04502708A/ja active Pending
- 1990-01-12 AU AU50382/90A patent/AU650846B2/en not_active Ceased
- 1990-01-12 KR KR1019900702060A patent/KR910700334A/ko not_active Application Discontinuation
- 1990-01-12 EP EP19900902870 patent/EP0454778A4/en not_active Withdrawn
- 1990-01-16 CA CA002007816A patent/CA2007816A1/en not_active Abandoned
- 1990-01-16 IE IE17490A patent/IE63274B1/en not_active IP Right Cessation
- 1990-01-17 GR GR900100025A patent/GR900100025A/el unknown
- 1990-01-17 PT PT92884A patent/PT92884B/pt not_active IP Right Cessation
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WO1988009380A1 (en) * | 1987-05-28 | 1988-12-01 | Scripps Clinic And Research Foundation | Antibody combining sites that exhibit stereoselective synthase activity, and methods using the same |
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Also Published As
Publication number | Publication date |
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AU650846B2 (en) | 1994-07-07 |
EP0454778A1 (en) | 1991-11-06 |
JPH04502708A (ja) | 1992-05-21 |
FI95928C (fi) | 1996-04-10 |
FI95928B (fi) | 1995-12-29 |
WO1990008185A1 (en) | 1990-07-26 |
IE900174L (en) | 1990-07-17 |
IE63274B1 (en) | 1995-04-05 |
FI913427A0 (fi) | 1991-07-16 |
AU5038290A (en) | 1990-08-13 |
KR910700334A (ko) | 1991-03-14 |
PT92884B (pt) | 1995-12-29 |
PT92884A (pt) | 1990-07-31 |
CA2007816A1 (en) | 1990-07-17 |
GR900100025A (el) | 1991-06-07 |
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