Enzypep B.v.

Dsm IP Assets B.v.

Tibotec Pharmaceuticals Ltd.

Janssen Sciences Ireland Uc

Fresenius Kabi Ipsum S.r.l.

Covestro B.v.

Peter Jan Leonard Mario Quaedflieg

Timo Nuijens

Ana Toplak

Bart Rudolf Romanie Kesteleyn

Jan Metske Van Der Laan

Theodorus Sonke

Robert Jan Vijn

Franciscus Alphons Marie Lommen

Dirk Barend Janssen

Claudia Cusan

Bian Wu

Aylvin Jorge Angelo Athanasius Dias

Harold Monro Moody

Theodorus Johannes Godfried Maria Van Dooren

Constantinus Simon Maria Liebregts

Bartholomeus Johannes Margretha Plum

Dominique Louis Nestor Surleraux

Roel Wim Wiertz

Jacob Hermanus Matheus Hero Kooistra

Danniël Adrianus Franciscus Jacobus Boxtel Van

Adolf Fritiz Volker Wagner

Adolf Fritz Volker Wagner

Catharina Hubertina Maria Schepers

Quirinus Bernardus Broxterman

Van Theodorus Johannes Godfried Maria Dooren

Gerardus Karel Maria Verzijl

A method for synthesizing a peptide having the sequence His-X-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Y-Glu-Phe-Ile-Ala-Trp-Leu-Val-Z-Gly-Arg-Gly is disclosed. The method includes enzymatically coupling:

Chemo-enzymatic synthesis of semaglutide, liraglutide and GLP-1

Chemo-enzymatic synthesis of Semaglutide, Liraglutide and GLP-1

The invention relates to a method for preparing a coupling product having the sequence P-W-His-X-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Y-Glu-Phe-Ile-Ala-Trp-Leu-Val-Z-Gly-Arg-Gly. The method includes enzymatically coupling

The invention further relates to a process for the enzymatic synthesis of an (oligo)peptide. The invention relates to a method for designing an enzymatic synthesis process of an (oligo)peptide, comprising identifying two or more (oligo)peptide fragments of an (oligo)peptide, which fragments are (oligo)peptides suitable for preparing the (oligo)peptide by enzymatic condensation of the two or more peptide fragments using a ligase. The invention relates to a method for designing an enzymatic synthesis process of a cyclic (oligo)peptide, comprising identifying a non-cyclic (oligo)peptide from which the cyclic (oligo)peptide can be prepared by cyclisation, catalysed by a cyclase. The invention further relates to a process for the enzymatic synthesis of an (oligo)peptide.

Designing an enzymatic peptide fragment condensation strategy

The invention relates to a subtilisin BPN' variant or homolog thereof, having the following mutations compared to subtilisin BPN&#x2032; represented by SEQUENCE ID NO: 2 or a homolog sequence thereof:&#x2014;a deletion of the amino acids corresponding to positions 75-83;&#x2014;a mutation at the amino acid position corresponding to S221, the mutation corresponding to S221C or S221 selenocysteine, preferably S221C;&#x2014;at least one further mutation selected from the group consisting of amino acid positions corresponding to F189W, F189Y, S33D, S33T, N218D, N218T, N218E, N62D, N62S, N62W, and N62Y; preferably a mutation at the amino acid position corresponding to P225; wherein the amino acid positions are defined according to the sequence of subtilisin BPN&#x2032; represented by SEQUENCE ID NO: 2. The invention further relates to enzymatically synthesizing a peptide.

Subtilisin variants having a mutation in the S2 or S2# pocket

The invention relates to a method for enzymatically synthesizing an (oligo)peptide, comprising coupling (a) an (oligo)peptide C-terminal ester or thioester and (b) an (oligo)peptide nucleophile having an N-terminally unprotected amine, Further, the invention relates to an enzyme suitable for use as a catalyst in a method of the invention.

Peptide fragment condensation and cyclisation using a subtilisin variant with improved synthesis over hydrolysis ratio

The invention relates to a method for enzymatically synthesizing an (oligo)peptide, comprising coupling (a) an (oligo)peptide C-terminal ester or thioester and (b) an (oligo)peptide nucleophile having an N-terminally unprotected amine, wherein the coupling is carried out in a fluid comprising water, and wherein the coupling is catalyzed by a subtilisin BPN' variant or a homo-log thereof, which comprises the following mutations compared to subtilisin BPN&#x2032; represented by SEQUENCE ID NO: 2 or a homolog sequence thereof: a deletion of the amino acids corresponding to positions 75-83; a mutation at the amino acid position corresponding to S221, the mutation being S221C or S221 selenocysteine; preferably a mutation at the amino acid position corresponding to P225 wherein the amino acid positions are defined according to the sequence of subtilisin BPN&#x2032; represented by SEQUENCE ID NO: 2. Further, the invention relates to an enzyme suitable for use as a catalyst in a method of the invention.

Method for enzymatically synthesizing an oligopeptide, comprising the coupling of an (optionally N-protected) protected oligopeptide ester with an (optionally C-protected) protected oligopeptide nucleophile in an organic solvent or an organic solvent mixture having a water content of 0.1 vol % or less, by a subtilisin in any possible form.

Side-chain protected oligopeptide fragment condensation using subtilisins in organic solvents

Compounds and polymers obtained from such compounds are provided, wherein the compounds have (a) at least two polymerizable moieties, (b) at least one amino acid residue of an amino acid comprising at least two amine groups of which at least two amine groups have formed a carbamate, a thiocarbamate or a carbamide group, and (c) a biomolecular moiety linked directly or via a spacer to the carboxylic acid moiety of the diamino acid residue or a carboxylic acid to which such moiety can be linked.

Carbamate, thiocarbamate or carbamide comprising a biomolecular moiety

The invention relates to a method for synthesizing a peptide by enzymatically preparing an ester or thioester from (i) an N-terminal protected amino acid or an N-terminal protected peptide where either can have a protected C-terminal ester group and (ii) an alcohol represented by the formula HO&#x2014;CX&#x2014;Z or a thiol represented by the formula HS&#x2014;CX&#x2014;Z, each X independently representing a halogen atom or a hydrogen atom; and Z represents an electron withdrawing group comprising at least one sp-hybridized carbon comprising at least two substituents comprising a heteroatom directly attached to the at least one sp-hybridized carbon or at least one sp-hybridized carbon comprising one or two substituents comprising a heteroatom directly attached to the at least one sp-hybridized carbon, and enzymatically coupling the prepared ester or thioester with an optionally C-terminal protected amino acid or with an optionally C-terminal protected peptide in a medium comprising 2 wt. % water or less.

Peptide synthesis using enzymatic activation and coupling

The invention relates to a method for preparing an optionally N-protected amino acid C-terminal ester or an optionally N-protected peptide C-terminal ester, comprising transesterifying the C-terminal t-alkyl ester of the amino acid or the C-terminal t-alkyl ester of the peptide with an alcohol (other than the t-alcohol corresponding to the t-alkyl group of the ester) in the presence of a hydrolytic enzyme (E.C. 3). The invention further relates to a method for preparing a peptide comprising coupling an activated, N-protected, amino acid C-terminal ester or an optionally N-protected peptide C-terminal ester with an optionally C-terminal protected amino acid or an optionally C-terminal protected peptide via a peptide bond, in the presence of an enzyme catalysing peptidic bond formation.

Chemo-enzymatic peptide synthesis via C-terminal ester interconversion

The present invention relates to methods for the preparation of diastereomerically pure (3R,3aS,6aR) hexahydro-furo[2,3-b]furan-3-ol as well as a novel intermediate, (3aR,4S,6aS) 4-methoxy-tetrahydro-furo[3,4-b]furan-2-one for use in said methods. More in particular the invention relates to a stereoselective method for the preparation of diastereomerically pure (3R,3aS,6aR) hexahydro-furo[2,3-b]furan-3-ol, as well as methods for the crystallization of (3aR,4S,6aS) 4-methoxy-tetrahydro-furo[3,4-b]furan-2-one and for the epimerization of (3aR,4R,6aS) 4-methoxy-tetrahydro-furo[3,4-b]-furan-2-one to (3aR,4S,6aS) 4-methoxy-tetrahydro-furo[3,4-b]furan-2-one.

Methods for the preparation of (3R,3aS,6aR) hexahydro-furo[2,3-b]furan-3-ol

The invention relates to a process for the preparation of (S)-glyceraldehyde acetonide in aqueous solution from 3,4-O-isopropylidene-L-threonic acid or a salt thereof in aqueous solution, and hypochlorite in aqueous solution wherein the aqueous hypochlorite solution has a pH&#x3e;7.5 and wherein during addition of at least 0.1 molar equivalents of hypochlorite based on the amount of 3,4-O-isopropylidene-L-threonic acid, an acid solution is not simultaneously added. The invention also relates to a process according to the invention, wherein 3,4-O-isopropylidene-L-threonic acid or a salt thereof is prepared from 5,6-O-isopropylidene-L-ascorbic acid or a salt thereof in the presence of HOand a base in a manner known per se, wherein excess HOis optionally removed by catalase. The invention also relates to a process according to the invention, wherein 5,6-O-isopropylidene-L-ascorbic acid or a salt thereof is prepared by reacting L-ascorbic acid or a salt thereof with an acetonide forming agent, preferably in the presence of an acid catalyst.

Process for the preparation of (S)-glyceraldehyde acetonide

A process for preparation of a compound with enhanced optical purity is disclosed wherein a mixture of the enantiomers of a chiral amine is brought into contact with an enzyme having peptide deformylase activity with a bivalent metal ion as a cofactor.

Process for the preparation of compounds with enhanced optical purity

The present invention relates to a method for the preparation of hexahydro-furo[2,3-b]furan-3-ol as well as novel intermediates for use in said method. More in particular the invention relates to a stereoselective method for the preparation of hexahydro-furo[2,3-b]furan-3-ol, and to a method amenable to industrial scaling up.

Growing community of inventors

Geleen, Netherlands

Peter Jan Leonard Mario Quaedflieg