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WO2002001223A1 - Approche substructurale pour l'obtention de polymeres a empreinte moleculaire presentant une selectivite elevee pour l'acide folique et ses analogues - Google Patents

Approche substructurale pour l'obtention de polymeres a empreinte moleculaire presentant une selectivite elevee pour l'acide folique et ses analogues Download PDF

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Publication number
WO2002001223A1
WO2002001223A1 PCT/SE2001/001483 SE0101483W WO0201223A1 WO 2002001223 A1 WO2002001223 A1 WO 2002001223A1 SE 0101483 W SE0101483 W SE 0101483W WO 0201223 A1 WO0201223 A1 WO 0201223A1
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WO
WIPO (PCT)
Prior art keywords
analogues
template
folic acid
molecularly imprinted
approach
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.)
Ceased
Application number
PCT/SE2001/001483
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English (en)
Inventor
Börje SELLERGREN
Milena Quaglia
Karine Chenon
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.)
MIP Technologies AB
Original Assignee
MIP Technologies AB
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 MIP Technologies AB filed Critical MIP Technologies AB
Priority to AU2001267970A priority Critical patent/AU2001267970A1/en
Publication of WO2002001223A1 publication Critical patent/WO2002001223A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/82—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving vitamins or their receptors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2600/00—Assays involving molecular imprinted polymers/polymers created around a molecular template

Definitions

  • MIPs Molecularly imprinted polymers
  • the technique shows promise in chiral separations of for example amino acid derivatives, peptides, phosphonates, aminoalcohols and beta-blocking compounds, affinity chromatography of nucleotides and the DNA-bases as well as substitute for antibodies in immunoassays or extractions of commercial drugs.
  • MI Molecular imprinting
  • the separation can be through an affinity chromatographic procedure where pH, ion strength or solvent gradients can be used in order to control the strength of interaction with the stationary phase.
  • the separation can target enantiomers or diastereomers in a mixture of enantiomers or diastereomers of one or many compounds.
  • Analytical applications can in addition to the above mentioned separations be: competetitive binding assays, chemical sensors or selective sample enrichments . 1
  • the materials can be synthesized in any standard equipped laboratory in a relatively short time and some of the MIPs exhibit binding affinities and selectivities in the order of those exhibited by antibodies towards their antigens.
  • Most MIPs are synthesized by free radical polymerization of functional monounsaturated (vinylic, acrylic, methacrylic) monomers and an excess of crosslinking di- or tri- unsaturated (vinylic, acrylic, methacrylic) monomers resulting in porous organic network materials.
  • These polymerizations have the advantage of being relatively robust allowing polymers to be prepared in high yield using different solvents (aqueous or organic) and at different temperatures. This is necessary in view of the varying solubilities of the template molecules.
  • the most successful noncovalent imprinting systems are based on commodity acrylic or methacrylic monomers, such as methacrylic acid (MAA) , crosslinked with ethyleneglycol dimethacrylate (EDMA) .
  • MAA methacrylic acid
  • EDMA ethyleneglycol dimethacrylate
  • L-PA L-phenylalanine anilide
  • the template (L-PA) , the functional monomer (MAA) and the crosslinking monomer (EDMA) are dissolved in a poorly hydrogen bonding solvent (diluent) of low to medium polarity.
  • the free radical polymerization is then initiated with an azo initiator, commonly azo-N,N' -bis-isobutyronitrile (AIBN) either by photochemical homolysis below room temperature or thermochemically at 60°C or higher.
  • AIBN azo-N,N' -bis-isobutyronitrile
  • the resultant polymer is crushed by mortar and pestle or in a ball mill, extracted by a Soxhlet apparatus, and sieved to a particle size suitable for chromatographic
  • the polymers are then evaluated as stationary phases in chromatography by comparing the retention time or capacity factor (k' ) of the template with that of structurally related analogs.
  • This invention describes the synthesis of a new class of molecularly imprinted polymers capable of recognizing folic acid and its analogues ( Figure 2) .
  • Figure 2 For this purpose specially designed templates and functional monomers have been used.
  • the poor solubility and stability of these templates require alternative approaches to be developed.
  • substructures of these compounds may be targeted using organic soluble analogues or newly designed monomers .
  • Particularly strong binding was obtained when using methacrylic acid as the functional monomer and organic soluble diaminopteridine analogues as templates ( Figure 3) , thus targeting the pteridine ring system.
  • analogues can be 2 , 4-diamino-6, 7-diisopropylpteri- dine (DIP) , trimethopriim (TRP) or trimetrexate (TRX) .
  • DIP diisopropylpteri- dine
  • TRP trimethopriim
  • TRX trimetrexate
  • the polymer is synthesized by free radical polymerization of a mixture of methacrylic acid or other functional monomer, and a crosslinking monomer, that can be ethyleneglycoldimethacrylate or trimethylolpropane- trimethacrylate, in presence of a solvent and a template and an initiator, that can be azobisisobutyronitrile.
  • the template can be 2 , 4-diamino-6, 7-diisopropylpteridine (DIP) , trimethoprim (TRP) or trimetrexate (TRX) . ( Figure 3) After polymerization the polymer is freed from the template by a washing procedure and can then be used for selective separations.
  • the polymer is synthesized by free radical polymerization of a mixture of a formamidine or any of the functional monomers in Figure 4, targeting the glutamic acid side chain, and a crosslinking monomer, that can be ethyleneglycoldimethacrylate or trimethylolpropanetrimeth- acrylate, in presence of a solvent and a template and an initiator, that can be azobisisobutyronitrile.
  • the template can be Glutamic acid or an analogue thereof, folic acid, methotrexate or leucovorine or analogues of these. After polymerization the polymer is freed from the template by a washing procedure and can then be used for selective separations.
  • the polymer prepared according to Example 1 and 2 can be used for separation of enantiomers or diastereomers of the template or for separation of the template or template analogues from structurally related compounds. This can be done by chromatography, capillary electrophoresis, capillary electrochromatography, batch modes or membrane modes .
  • the polymer can further be used for catalysing chemical reactions such as esterolysis, amidolysis, ester synthesis or amide synthesis or used in chemical sensors . Litterature

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Molecular Biology (AREA)
  • Hematology (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Cell Biology (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Steroid Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Treatment Of Liquids With Adsorbents In General (AREA)
  • Solid-Sorbent Or Filter-Aiding Compositions (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne des matrices et des monomères fonctionnels pouvant être utilisés pour produire des polymères à empreinte moléculaire en vue d'une reconnaissance sélective de l'acide folique et de ses analogues.
PCT/SE2001/001483 2000-06-28 2001-06-28 Approche substructurale pour l'obtention de polymeres a empreinte moleculaire presentant une selectivite elevee pour l'acide folique et ses analogues Ceased WO2002001223A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001267970A AU2001267970A1 (en) 2000-06-28 2001-06-28 Substructure approach to molecularly imprinted polymers with high selectivity for folic acid and analogues

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE0002463A SE0002463D0 (sv) 2000-06-28 2000-06-28 Substructure approach to moleculary imprinted polymers with high selectivity for folic acid and analogues
SE0002463-8 2000-06-28

Publications (1)

Publication Number Publication Date
WO2002001223A1 true WO2002001223A1 (fr) 2002-01-03

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PCT/SE2001/001483 Ceased WO2002001223A1 (fr) 2000-06-28 2001-06-28 Approche substructurale pour l'obtention de polymeres a empreinte moleculaire presentant une selectivite elevee pour l'acide folique et ses analogues

Country Status (3)

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AU (1) AU2001267970A1 (fr)
SE (1) SE0002463D0 (fr)
WO (1) WO2002001223A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004067578A1 (fr) * 2003-01-30 2004-08-12 Mip Technologies Ab Polymeres imprimes par voie moleculaire destines a l'extraction de composants de produits alimentaires
WO2006041398A1 (fr) * 2004-10-12 2006-04-20 Mip Technologies Ab Procede de production de polymeres a empreinte moleculaire destine a la reconnaissance de molecules cible
US20110002874A1 (en) * 2005-04-28 2011-01-06 Board Of Regents, The University Of Texas System Polymer Network Compositions and Associated Methods
CN104267087A (zh) * 2014-10-29 2015-01-07 安徽师范大学 一种电化学生物传感器,及其制备方法和用途
CN105693960A (zh) * 2016-03-03 2016-06-22 华南师范大学 一种谷氨酸表面分子印迹聚合物硅胶微球的制备方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999047531A1 (fr) * 1998-03-16 1999-09-23 Chiral Technologies, Inc. Separation chirale de pyrimidines

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999047531A1 (fr) * 1998-03-16 1999-09-23 Chiral Technologies, Inc. Separation chirale de pyrimidines

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
CONG YU ET AL.: "Enantiomeric recognition by molecularly imprinted polymers using hydrophobic interactions", ANALYTICAL LETTERS, vol. 30, no. 12, 1997, pages 2123 - 2140, XP002949451 *
CONG YU ET AL.: "Insights into the origins of binding and the recognition properties of molecularly imprinted polymers prepared using an amide as the hydrogen-bonding functional group", JOURNAL OF MOLECULAR RECOGNITION, vol. 11, 1998, pages 69 - 74, XP002905461 *
LARS I. ANDERSSON ET AL.: "Enantiomeric resolution on molecularly imprinted polymers prepared with only non-covalent and non-ionic interactions", JOURNAL OF CHROMATOGRAPHY, vol. 516, 1990, pages 313 - 322, XP002949450 *
MARIA KEMPE ET AL.: "Chiral separation using molecularly imprinted heteroaromatic polymers", JOURNAL OF MOLECULAR RECOGNITION, vol. 6, 1993, pages 25 - 29, XP002949454 *
MASAKAZU YOSHIKAWA ET AL.: "Alternative molecularly imprinted membranes from a derivative of natural polymer, cellulose acetate", JOURNAL OF APPLIED POLYMER SCIENCE, vol. 72, 1999, pages 493 - 499, XP002949452 *
MILENA QUAGLIA ET AL.: "Target analogue imprinted polymers with affinity for folic acid and related compounds", J. AM. CHEM. SOC., vol. 123, 2001, pages 2146 - 2154, XP002949449 *
SHOUZHUO YAO ET AL.: "Biomimetic bulk acoustic wave sensor for determination of trimethoprim in the organic phase based on a molecular imprinting polymer", ANALYTICAL SCIENCES, vol. 16, February 2000 (2000-02-01), pages 211 - 215, XP002949453 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004067578A1 (fr) * 2003-01-30 2004-08-12 Mip Technologies Ab Polymeres imprimes par voie moleculaire destines a l'extraction de composants de produits alimentaires
US7750090B2 (en) 2003-01-30 2010-07-06 Mip Technologies Ab Moleculary imprinted polymers for extraction of components from foodstruffs
WO2006041398A1 (fr) * 2004-10-12 2006-04-20 Mip Technologies Ab Procede de production de polymeres a empreinte moleculaire destine a la reconnaissance de molecules cible
US20110002874A1 (en) * 2005-04-28 2011-01-06 Board Of Regents, The University Of Texas System Polymer Network Compositions and Associated Methods
CN104267087A (zh) * 2014-10-29 2015-01-07 安徽师范大学 一种电化学生物传感器,及其制备方法和用途
CN105693960A (zh) * 2016-03-03 2016-06-22 华南师范大学 一种谷氨酸表面分子印迹聚合物硅胶微球的制备方法
CN105693960B (zh) * 2016-03-03 2018-07-17 华南师范大学 一种谷氨酸表面分子印迹聚合物硅胶微球的制备方法

Also Published As

Publication number Publication date
AU2001267970A1 (en) 2002-01-08
SE0002463D0 (sv) 2000-06-28

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