EP0454778A4 - Molecules with antibody combining sites that exhibit stereospecific catalysis - Google Patents

Molecules with antibody combining sites that exhibit stereospecific catalysis

Info

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Withdrawn
Application number
EP19900902870
Other languages
English (en)
Other versions
EP0454778A1 (en
Inventor
Richard Lerner
Kim Janda
Stephen Benkovic
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Scripps Research Institute
Original Assignee
Scripps Clinic and Research Foundation
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Scripps Clinic and Research Foundation filed Critical Scripps Clinic and Research Foundation
Publication of EP0454778A1 publication Critical patent/EP0454778A1/en
Publication of EP0454778A4 publication Critical patent/EP0454778A4/en
Withdrawn legal-status Critical Current

Links

Classifications

    • 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.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Medicinal Chemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Cell Biology (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
EP19900902870 1989-01-17 1990-01-12 Molecules with antibody combining sites that exhibit stereospecific catalysis Withdrawn EP0454778A4 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US297798 1981-08-31
US29779889A 1989-01-17 1989-01-17

Publications (2)

Publication Number Publication Date
EP0454778A1 EP0454778A1 (en) 1991-11-06
EP0454778A4 true EP0454778A4 (en) 1993-10-06

Family

ID=23147792

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19900902870 Withdrawn EP0454778A4 (en) 1989-01-17 1990-01-12 Molecules with antibody combining sites that exhibit stereospecific catalysis

Country Status (10)

Country Link
EP (1) EP0454778A4 (ko)
JP (1) JPH04502708A (ko)
KR (1) KR910700334A (ko)
AU (1) AU650846B2 (ko)
CA (1) CA2007816A1 (ko)
FI (1) FI95928C (ko)
GR (1) GR900100025A (ko)
IE (1) IE63274B1 (ko)
PT (1) PT92884B (ko)
WO (1) WO1990008185A1 (ko)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of WO9008185A1 *

Also Published As

Publication number Publication date
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

Similar Documents

Publication Publication Date Title
US4900674A (en) Antibody combining sites that exhibit amide or ester synthase activity
US4659567A (en) Molecules with antibody combining sites that bind to hydrolytic transition states
AU620019B2 (en) Molecules with antibody combining sites that exhibit catalytic properties
US5126258A (en) Molecules with antibody combining sites that exhibit catalytic properties
US5079152A (en) Antibody combining sites that exhibit stereoselective synthase activity, and methods using the same
US5187086A (en) Molecules with antibody combining sites that catalyze hydrolysis reactions through use of a charged hapten
AU650419B2 (en) Polyvalent metal ion-containing antibody combining site catalysts
AU650846B2 (en) Molecules with antibody combining sites that exhibit stereospecific catalysis
US5248611A (en) Stereoisomer separation method using antibody combing site-containing molecules
US5208152A (en) Catalysts of diels-alder reactions, methods and catalysts therefor
US5444155A (en) Molecules with antibody combining sites that induce asymmetry
US5250426A (en) Molecules with antibody combining sites that induce asymmetry
US5384252A (en) Molecules with antibody combining sites that catalyze carbocyclic ring formation from 5,6-ethylenically unsaturated sulfonate molecules
US5429941A (en) Process for antibody combining site-catalyzed epoxide formation from 1-benzyl-1-hydrocarbyl alkene molecules
US5478728A (en) Process for antibody combining site-catalyzed SYN elimination in the formation of a CIS olefin

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19910724

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB IT LI LU NL SE

A4 Supplementary search report drawn up and despatched

Effective date: 19930820

AK Designated contracting states

Kind code of ref document: A4

Designated state(s): AT BE CH DE DK ES FR GB IT LI LU NL SE

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: THE SCRIPPS RESEARCH INSTITUTE

17Q First examination report despatched

Effective date: 19960110

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 19971211