EP3433374A1 - Glycosylierte mono(2-hydroxyethyl) terephthalsäure und glycosylierte bis(2-hydroxyethyl) terephthalsäure - Google Patents

Glycosylierte mono(2-hydroxyethyl) terephthalsäure und glycosylierte bis(2-hydroxyethyl) terephthalsäure

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Publication number
EP3433374A1
EP3433374A1 EP17713276.8A EP17713276A EP3433374A1 EP 3433374 A1 EP3433374 A1 EP 3433374A1 EP 17713276 A EP17713276 A EP 17713276A EP 3433374 A1 EP3433374 A1 EP 3433374A1
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EP
European Patent Office
Prior art keywords
mhet
bhet
compound according
hydroxyethyl
compound
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.)
Pending
Application number
EP17713276.8A
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German (de)
English (en)
French (fr)
Inventor
Jürgen SEIBEL
Malte TIMM
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Julius Maximilians Universitaet Wuerzburg
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Julius Maximilians Universitaet Wuerzburg
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Application filed by Julius Maximilians Universitaet Wuerzburg filed Critical Julius Maximilians Universitaet Wuerzburg
Publication of EP3433374A1 publication Critical patent/EP3433374A1/de
Pending legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P19/00—Preparation of compounds containing saccharide radicals
    • C12P19/44—Preparation of O-glycosides, e.g. glucosides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/18—Acyclic radicals, substituted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y301/00—Hydrolases acting on ester bonds (3.1)
    • C12Y301/01—Carboxylic ester hydrolases (3.1.1)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
    • C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
    • C12Y302/0102—Alpha-glucosidase (3.2.1.20)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
    • C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
    • C12Y302/01021—Beta-glucosidase (3.2.1.21)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
    • C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
    • C12Y302/01023—Beta-galactosidase (3.2.1.23), i.e. exo-(1-->4)-beta-D-galactanase
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
    • C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
    • C12Y302/0108—Fructan beta-fructosidase (3.2.1.80)
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02W—CLIMATE CHANGE MITIGATION TECHNOLOGIES RELATED TO WASTEWATER TREATMENT OR WASTE MANAGEMENT
    • Y02W30/00—Technologies for solid waste management
    • Y02W30/50—Reuse, recycling or recovery technologies
    • Y02W30/62—Plastics recycling; Rubber recycling

Definitions

  • glycosylated compounds according to the invention have advantageous surface properties. Because of these properties, the compounds according to the invention can be used in a variety of ways, such as cell culture substrates.
  • the glycosylation of the compounds of the present invention favors their biodegradability and biocompatibility.
  • the compounds of the invention can advantageously be used according to the invention in medical applications, in particular in biomedical applications.
  • a compound comprising mono (2-hydroxyethyl) terephthalic acid (MHET) or bis (2-hydroxyethyl) terephthalic acid chemically bound to a saccharide.
  • a compound according to embodiment 5, wherein the monosaccharide or disaccharide is selected from a group containing hexoses and pentoses.
  • a compound according to embodiment 10 wherein the enzymatic glycosylation is catalyzed by a glucosidase.
  • PET polyethylene terephthalate
  • PET polyethylene terephthalate
  • a compound according to embodiment 13 or 14, wherein the enzymatic degradation of PET is catalyzed by a hydrolase.
  • a compound according to embodiment 15, wherein the hydrolase is PETase from Idionella sakaiensis.
  • a compound according to embodiment 15 or 16, wherein the hydrolase comprises the amino acid sequence shown in SEQ ID NO: 1.
  • a compound according to any one of embodiments 13 to 17, wherein the enzyme for the enzymatic glycosylation of MHET or BHET and the enzyme are used together for the enzymatic degradation of PET.
  • a compound according to embodiment 18, wherein a microorganism harboring the enzyme for enzymatic glycosylation and the enzyme for enzymatic degradation of PET is used.
  • Ri comprises a glycosidic bond-bound saccharide
  • R 2 comprises a glycosidic bond-bound saccharide or H.
  • Ri comprises a glycosidic bond-bound saccharide and R2 comprises a methacrylic residue.
  • R2 comprises a methacrylic residue.
  • Ri comprises a glycosidic bond-bound saccharide and R2 comprises a lipophilic side chain, preferably a saturated or unsaturated aliphatic hydrocarbon side chain, or a linker.
  • R 2 is a C 5 to C 20 saturated or unsaturated aliphatic hydrocarbon side chain, preferably a saturated or unsaturated C 5 to C 15 aliphatic hydrocarbon side chain, more preferably a Cs to C 12 saturated or unsaturated aliphatic hydrocarbon side chain, more preferably a saturated or unsaturated aliphatic C 10 Hydrocarbon side chain and more preferably a saturated aliphatic C10 hydrocarbon side chain is.
  • a compound according to embodiment 28 selected from a compound having the following structure (a) to (j):
  • n 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.
  • MHET mono (2-hydroxyethyl) terephthalic acid
  • BHET bis (2-hydroxyethyl) terephthalic acid
  • PET polyethylene terephthalate
  • the method according to embodiment 44, wherein the hydrolase is PETase from Idionella sakaiensis.
  • a method according to embodiment 44 or 45, wherein the hydrolase comprises the amino acid sequence shown in SEQ ID NO: 1.
  • a methacrylic residue is chemically bonded to the glycosylated MHET or BHET, the methacrylic residue being preferentially bound by enzymatic esterification to the glycosylated MHET or BHET, wherein the enzymatic esterification is preferably catalyzed by a lipase.
  • the methacrylic radical is chemically bound to the glycosylated MHET or BHET by addition of vinylmethyl methacrylate.
  • a lipophilic side chain preferably a saturated or unsaturated aliphatic hydrocarbon side chain
  • a lipophilic side chain preferably a saturated or unsaturated aliphatic hydrocarbon side chain
  • the lipophilic side chain a saturated or unsaturated C 5 to C 20 hydrocarbon side chain, preferably a saturated or unsaturated C 5 to C 15 hydrocarbon side chain, more preferably a saturated or unsaturated Cs-C12 hydrocarbon side chain, more preferably a saturated or unsaturated C10 hydrocarbon side chain and particularly preferably a saturated C10 hydrocarbon side chain.
  • the polymer of embodiment 56, wherein the polymer is a bio-hybrid polymer.
  • Microorganism harboring at least one enzyme for the enzymatic glycosylation of MHET and / or BHET and at least one enzyme for the enzymatic degradation of PET.
  • a microorganism according to embodiment 58 wherein the microorganism is a recombinant microorganism and the enzyme for the enzymatic glycosylation of MHET and / or BHET and / or the enzyme for the enzymatic degradation of PET is a recombinant enzyme.
  • the microorganism according to any one of the embodiments 58 to 62, wherein the enzyme for enzymatic degradation of PET is a hydrolase.
  • a microorganism according to embodiment 63, wherein the hydrolase is PETase from Idionella sakaiensis.
  • the microorganism according to embodiment 63 or 64, wherein the hydrolase comprises the amino acid sequence shown in SEQ ID NO: 1.
  • MHET mono (2-hydroxyethyl) terephthalic acid
  • bis (2-hydroxyethyl) terephthalic acid to produce MHET or bis (2-hydroxyethyl) terephthalic acid by bacterial degradation or enzymatic degradation from PET.
  • MHET mono (2-hydroxyethyl) terephthalic acid
  • 68. A compound according to embodiments 66 and 67, wherein the MHET or bis (2-hydroxyethyl) terephthalic acid and the saccharide are chemically bonded to each other via a glycosidic bond.
  • Fig. 1 Figure: U. Bornscheuer, Science 351, 1 154 (2016); Degradation of PET by /. sakaiensis.
  • FIG. 2 Exemplary representation of the glucosylation of PET obtained.
  • Fig. 3 A biohybrid polymer of glucosylated MHET.
  • Fig. 4 Glycosylated MHET serves as an active ingredient, fine chemical or the synthesis of polymers.
  • Fig. 5 Exemplary structure of a biohybrid polymer of glucosylated MHET or bis (2-hydroxyethyl) terephthalic acid.
  • Fig. 6 Glycosylated MHET and glycosylated bis (2-hydroxyethyl) terephthalic acid can be linked to methacrylate.
  • methacrylate is enzymatically esterified with one or more alcohol functions of MHET or bis (2-hydroxyethyl) terephthalic acid.
  • FIG. 7 Glycosylated MHET and glycosylated bis (2-hydroxyethyl) terephthalic acid can be linked to methacrylate.
  • methacrylate is enzymatically esterified with one or more alcohol functions of MHET or bis (2-hydroxyethyl) terephthalic acid.
  • Fig. 8 Synthesized glycosylated BHET methacrylates and glycosylated MHET methacrylates can be prepared by means of a radical initiator, e.g. Polymerize potassium peroxodisulfate.
  • a radical initiator e.g. Polymerize potassium peroxodisulfate.
  • Figure 9 Synthesized glycosylated BHET methacrylates and glycosylated MHET methacrylates can be prepared with the aid of a radical initiator, e.g. Polymerize potassium peroxodisulfate.
  • a radical initiator e.g. Polymerize potassium peroxodisulfate.
  • Fig. 10 Synthesized glycosylated BHET methacrylates and glycosylated MHET methacrylates can be prepared with the aid of a radical initiator, e.g. Polymerize potassium peroxodisulfate.
  • a radical initiator e.g. Polymerize potassium peroxodisulfate.
  • Glycosylated MHET and glycosylated bis (2-hydroxyethyl) terephthalic acid may also be linked to aliphatic alcohols.
  • aliphatic alcohols e.g. Dodecanol enzymatically esterified with ⁇ - ⁇ -Glc.
  • Fig. 12 Thiols, amines and other alcohols are also conjugated with glycosylated BHET instead of the decanol.
  • FIG. 13 Exemplary representation of the structure of ⁇ -glycosylated MHET.
  • FIG. Fig. 14 Exemplary representation of the structure of MHET.
  • FIG. 15 Exemplary representation of the structure of ⁇ -glycosylated MHET.
  • Fig. 16 1 H-NMR spectrum of .beta.-glycosylated MHET.
  • Fig. 17 13 C-NMR spectrum of .beta.-glycosylated MHET.
  • FIG. 18 Exemplary representation of the structure of di-1,3- ⁇ -glucosylated MHET.
  • Fig. 19 Exemplary representation of the structure of ⁇ -galactosylated MHET.
  • Fig. 20 1 H-NMR spectrum of ⁇ -galactosylated MHET.
  • Fig. 21 13 C-NMR spectrum of beta-galactosylated MHET.
  • Fig. 22 Exemplary representation of the structure of ⁇ -glucosylated bis (2-hydroxyethyl) terephthalate.
  • FIG. 23 1 H-NMR spectrum of ⁇ -glucosylated bis (2-hydroxyethyl) terephthalate.
  • Fig. 24 13 C-NMR spectrum of ⁇ -glucosylated bis (2-hydroxyethyl) terephthalate.
  • FIG. 25 Exemplary representation of the structure of di-1,6-glucosylated bis (2-hydroxyethyl) terephthalate.
  • FIG. 26 1 H-NMR spectrum of di-1,6-glucosylated bis (2-hydroxyethyl) terephthalate.
  • FIG. 27 13 C-NMR spectrum of di-1,6-glucosylated bis (2-hydroxyethyl) terephthalate.
  • Fig. 28 Exemplary representation of the structure of ⁇ -glucosylated bis (2-hydroxyethyl) terephthalate.
  • Fig. 29 1 H-NMR spectrum of ⁇ -glucosylated bis (2-hydroxyethyl) terephthalate.
  • Fig. 30 13 C-NMR spectrum of ⁇ -glucosylated bis (2-hydroxyethyl) terephthalate.
  • Fig. 31 Exemplary representation of the structure of ⁇ -galactosylated bis (2-hydroxyethyl) terephthalate.
  • FIG. 32 1 H-NMR spectrum of ⁇ -galactosylated bis (2-hydroxyethyl) terephthalate.
  • Fig. 33 13 C-NMR spectrum of ⁇ -galactosylated bis (2-hydroxyethyl) terephthalate.
  • FIG. 34 Exemplary representation of the structure of di- ⁇ -glucosylated bis (2-hydroxyethyl) terephthalate.
  • FIG. 35 1 H-NMR spectrum of di- ⁇ -glucosylated bis (2-hydroxyethyl) terephthalate.
  • FIG. 36 13 C-NMR spectrum of di- ⁇ -glucosylated bis (2-hydroxyethyl) terephthalate.
  • Fig. 37 Exemplary representation of the structure of glycosylated MA-BHET- ⁇ -Glc.
  • Fig. 38 1 H-NMR spectrum of glycosylated MA-BHET- ⁇ -Glc.
  • Fig. 39 13 C-NMR spectrum of glycosylated MA-BHET- ⁇ -Glc.
  • FIG. 40 Exemplary representation of the structure of glycosylated MA 2 -BHET- ⁇ -
  • Fig. 41 1 H-NMR spectrum of glycosylated MA 2 -BHET-a-Glc.
  • Fig. 42 13 C-NMR spectrum of glycosylated MA 2 -BHET-a-Glc.
  • FIG. 43 Exemplary representation of the structure of glycosylated a-Glc-MHET
  • Figure 44 1 H-NMR spectrum of glycosylated ⁇ -Glc-MHET decanol.
  • Figure 45 13 C NMR spectrum of glycosylated ⁇ -Glc-MHET decanol.
  • Fig. 46 Exemplary representation of the structure of ⁇ -glucosylated MHET.
  • Fig. 47 1 H-NMR spectrum of ⁇ -glucosylated MHET.
  • Fig. 48 13 C-NMR spectrum of ⁇ -glucosylated MHET.
  • Fig. 49 detection of the polymer; shown is the 1 H-NMR spectrum of the polymer.
  • Fig. 50 Exemplary 13 C NMR spectrum of MHET shown
  • the term “compound” is used herein as it would be understood by those skilled in the art, ie, meaning in particular "chemical compound”.
  • the term “compound comprising glycosylated mono (2-hydroxyethyl) terephthalic acid (MHET) or glycosylated bis (2-hydroxyethyl) terephthalic acid (BHET)” is to be understood that with the respective mono (2-hydroxyethyl) terephthalic acid (MHET) or Bis (2-hydroxyethyl) terephthalic acid (BHET) is also optionally meant esters, amides, thioesters and ethers of the respective mono (2-hydroxyethyl) terephthalic acid (MHET) or bis (2-hydroxyethyl) terephthalic acid (BHET) are esters, amides, thioesters and ethers of the respective mono (2-hydroxyethyl) terephthalic acid (MHET) or bis (2-hydroxyethyl) tere
  • a glycosidic bond can be formed by enzymatic glycosylation.
  • Enzymatic glycosylation can be catalyzed by a glycosidase
  • glycosidases belong to the enzyme class of hydrolases and are classified under EC 3.2.1.
  • Glycosidases can reversibly hydrolyze a- or ß-glycosidic bonds.
  • the acceptor is typically first glycosylated. If enough monoglycosylated acceptor is present in the reaction mixture, multiple glycosylations can occur.
  • glycosidases for the enzymatic syntheses can be used, for example: ⁇ -glucosidase (sucrose isomerase): in suspension of microorganisms (Protaminobacter rubrum Z 12 (CBD 574.77)). It can preferably be used for the monoglucosylation.
  • the lipase Novozymes 435 can be used for enzymatic esterification or transesterification.
  • All compounds of the invention may be isolated. Accordingly, all processes according to the invention preferably comprise isolating the respective compound.
  • the silica gel is used in a solvent mixture of ethyl acetate: isopropanol: water (volume ratio 6: 3: 1), in the case of nonpolar substances, a mixture of ethyl acetate: methanol (volume ratio 12: 1) is used, the mixture is padded and the column is filled. Subsequently, the reaction mixture is dissolved in as little eluent as possible (preferably 1 g in 1 ml) and added to the column. The separation is carried out by elution with the eluent. The eluate is collected in vessels (a 10 mL) and determined by HPLC in which vessels the product is contained. The vessels are combined with product and the solvents are evaporated. A solid is obtained. embodiments
  • MHET or bis (2-hydroxyethyl) terephthalic acid is glycosylated by means of an enzyme and a glycosubstrate.
  • glycosubstrate disaccharides (e.g., sucrose, lactose, maltose), oligosaccharides (maltooligosaccharides) or polysaccharides (dextran, fructo-oligosaccharides, chitin, mannan, cellulose) are used.
  • the preparation of glycosylated MHET or bis (2-hydroxyethyl) terephthalic acid can be carried out starting from MHET or bis (2-hydroxyethyl) terephthalic acid.
  • the compound according to the invention is characterized by a chemically bound to a saccharide MHET or bis (2-hydroxyethyl) terephthalic acid.
  • Glycosylated MHET or bis (2-hydroxyethyl) terephthalic acid can be used as an active ingredient.
  • Glycosylated MHET or bis (2-hydroxyethyl) terephthalic acid can also be polymerized to biohybrid polymers (see Fig. 3).
  • glycosidic bond in a glycoside is reversibly catalyzed in particular by glucosidases, wherein the glycon, in this case the saccharide, and the aglycone, here MHET or bis (2-hydroxyethyl) terephthalic acid, are liberated while consuming a water molecule.
  • Glycosylated MHET or bis (2-hydroxyethyl) terephthalic acid serves as fine chemical, active ingredient or starting material for biohybrid polymers (see Fig. 4).
  • a thermoplastic polymer produced from the polyester family can be obtained.
  • polycondensation of glycosylated MHET or bis (2-hydroxyethyl) terephthalic acid will give rise to a thermoplastic polymer from the polyester family.
  • a polyester can be prepared by transesterification of di- and monoglucosylated bis (2-hydroxyethyl) terephthalic acid with ethanediol. Since it is an equilibrium reaction, split-off ethanediol is distilled off. It comes to the accumulation of glycosylated bis (2-hydroxyethyl) terephthalic acid. Likewise, mono- and diglycosylated bis (2-hydroxyethyl) terephthalic acid is esterified with terephthalic acid directly to a polyester.
  • a biohybrid polymer of glucosylated MHET or bis (2-hydroxyethyl) terephthalic acid may adopt the structure of FIG.
  • glycosylated MHET and glycosylated bis (2-hydroxyethyl) terephthalic acid can be linked to methacrylate.
  • This is methacrylate enzymatically esterified with one or more alcohol functions of MHET or bis (2-hydroxyethyl) terephthalic acid (FIG. 6, FIG. 7).
  • ⁇ - ⁇ -Glc with vinylmethyl acrylate at 50 ° C and the lipase Novozymes 435 arises when using the solvent tert-butyl alcohol, the di-esterified product MA 2 -BHET-a-Glc and the glycosylated ⁇ - ⁇ - ⁇ - Glc ( Figure 6).
  • Glycosylated MHET and glycosylated bis (2-hydroxyethyl) terephthalic acid can also be linked to aliphatic alcohols.
  • aliphatic alcohols e.g. Decanol enzymatically esterified with ⁇ - ⁇ -Glc (Fig. 1 1).
  • tert-butanol preferably forms ⁇ -Glc-MHET-decanol when the solvent is used (FIG. 11).
  • thiols, amines and other alcohols can be conjugated with glycosylated BHET. This allows the introduction of different linkers, which i.a. Contain biotin or can be used for bioorthogonal click reactions for the construction of cell culture scaffolds (FIG. 12).
  • the monosaccharide is selected from a group containing pentoses and hexoses.
  • hexoses have a carbon backbone with six carbon atoms and basically differ by the nature of the carbonyl function.
  • a keto group In a non-terminal carbonyl function (Ri-C (O) -R 2 ), a keto group, one speaks of ketohexoses.
  • a terminal carbonyl function, an aldehyde group, is aldohexose.
  • Pentoses (C 5 H 10 O 5 ) have a carbon backbone with five carbon atoms.
  • the hexoses are preferably selected from a group containing ⁇ -glucose, ⁇ -glucose, ⁇ -fructose, ⁇ -fructose, ⁇ -mannose, ⁇ -mannose, ⁇ -galactose and ⁇ -galactose, N-acetylglucosamine, glucosamine, glucuronic acid , Depending on which saccharide is chemically bound to the MHET or bis (2-hydroxyethyl) terephthalic acid, the nomenclature of the compound differs.
  • the compound is ⁇ - or ⁇ -glucosylated MHET or bis (2-hydroxyethyl) terephthalic acid.
  • ⁇ - or ⁇ -galactose as chemically bound saccharide, this is referred to as ⁇ - or ⁇ -galactosylated MHET or bis (2-hydroxyethyl) terephthalic acid.
  • an ⁇ - or ⁇ -fructose is bound as a saccharide to the MHET, it is ⁇ - or ⁇ -fructosylated MHET or bis (2-hydroxyethyl) terephthalic acid.
  • the compound ⁇ -glycosylated MHET is preferably characterized by the structural formula shown in FIG.
  • a glycosidic linkage is made between the ⁇ -glucose and the MHET.
  • the bonding is particularly advantageously carried out selectively via the hydroxyl group of the MHET bonded to the 1 ' carbon atom.
  • the oxygen atom bridging the ⁇ -glucose with the MHET comes from the MHET.
  • this linkage-independently of the saccharide used- is preferably carried out selectively via the hydroxyl group of the MHET bound to the 1 ' carbon atom.
  • the enzyme used is responsible for the selectivity of the bond formation at the 1 'carbon atom.
  • MHET is shown by way of example in FIG. 14.
  • MHET 0.05 mol / L
  • sucrose 0.4 mol / L
  • a suspension of microorganisms Protaminobacter rubrum Z 12 ( CBS 574.77)
  • an ⁇ -glucosidase solution 100 U in phosphate buffer
  • Sucrose consists of aD-glucose and ß-D-fructose, which are linked via an a, ß-1, 2-glycosidic bond.
  • the microorganism Protaminobacter rubrum Z 12 contains an enzyme, an ⁇ -glucosidase. It catalyzes the cleavage of the sucrose used in aD-glucose and ß-D-fructose. The aD-glucose chemically binds to the MHET during the reaction.
  • test results of the embodiment with a suspension of microorganisms are as follows.
  • the product is confirmed by mass spectrometry (MT203).
  • MHET 0.05 mol / L
  • cellobiose 0.4 mol / L
  • ⁇ -glucosidase solution 100 U in Natnumacetatpuffer or phosphate buffer.
  • the cellobiose is a disaccharide of two ⁇ -1,4-glucosidically linked glucose molecules.
  • the enzyme ⁇ -glucosidase allows the degradation of cellobiose to glucose.
  • the glucose chemically binds to the MHET during the reaction.
  • an ⁇ -glucosidase solution 100 U in phosphate buffer is added.
  • Sucrose consists of ⁇ -D-glucose and ⁇ -D-fructose, which are linked via an ⁇ , ⁇ -1,2-glycosidic linkage.
  • the microorganism Protaminobacter rubrum Z 12 contains an enzyme, an ⁇ -glucosidase. It catalyses the cleavage of the sucrose used in ⁇ -D-glucose and ⁇ -D-fructose.
  • the ⁇ -D-glucose chemically binds to bis (2-hydroxyethyl) terephthalate during the reaction.
  • reaction mixture is shaken at a temperature of 37 ° C in a water bath. After optimal product formation, the reaction is stopped. The product ⁇ -glycosylated bis (2-hydroxyethyl) terephthalate is obtained.
  • the optimal product formation is determined by continuous sampling and thin-layer chromatography.
  • FIG. 23 ⁇ -glucosylated bis (2-hydroxyethyl) terephthalate is exemplified in FIG.
  • the cellobiose is a disaccharide of two ⁇ -1,4-glucosidically linked glucose molecules.
  • the enzyme ⁇ -glucosidase allows the degradation of cellobiose to glucose.
  • the glucose chemically binds to bis (2-hydroxyethyl) terephthalate during the reaction.
  • Di- ⁇ -glucosylated bis (2-hydroxyethyl) terephthalate Di- ⁇ -glucosylated bis (2-hydroxyethyl) terephthalate is exemplified in FIG.
  • the product is confirmed by mass spectrometry.
  • BHET 0.05 mol / L
  • sucrose 0.4 mol / L
  • a fructosidase solution 100 U in sodium acetate buffer
  • the fructosidase solution catalyzes the cleavage of the sucrose into ⁇ -D-glucose and ⁇ -D-fructose enzymatically.
  • the ß-D-fructose binds chemically to the BHET during the reaction.
  • the reaction mixture is shaken for this purpose also at a temperature of 37 ° C in a water bath. After optimal product formation, the reaction is stopped.
  • ⁇ -Glucosylated MHET (20 mg) is heated to 250 ° C for 50 sec. There is a gas generation. There remains a brown-white solid, which is partially suspended in water and dissolved. Thin-layer chromatography analysis (MeOH / CH 2 Cl 2 ) shows that a high-polymer substance is formed from the suspension and is also UV-active.
  • ⁇ -Glucosylated MHET is exemplified in FIG. Further experimental results are shown in Fig. 47, Fig. 48 and in the following tables.
  • the present invention is industrially applicable in a variety of ways.
  • the further use of degradation products from the hydrolysis of PET in the form of biohybrid polymers is made possible.
  • biohybrid polymers according to the invention have increased biocompatibility, compostability, and / or allow improved adhesion of cultured cells to surfaces.

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  • Enzymes And Modification Thereof (AREA)
EP17713276.8A 2016-03-23 2017-03-23 Glycosylierte mono(2-hydroxyethyl) terephthalsäure und glycosylierte bis(2-hydroxyethyl) terephthalsäure Pending EP3433374A1 (de)

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US20200332334A1 (en) 2020-10-22
WO2017162825A1 (de) 2017-09-28

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