CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS S.A. (Grèce)
Inventeur(s)
Barlos, Kleomenis
Barlos, Konstantinos
Gatos, Dimitrios
Vasileiou, Zoi
Abrégé
A process for preparing a GLP-1 or GLP-2 peptide, said process comprising coupling in solution at least a first fragment and at least a second fragment, wherein the coupling comprises reacting the carboxy terminal amino acid of the first fragment with the amino terminal amino acid of the second fragment, and wherein the carboxy terminal amino acid of the first fragment is other than a Gly residue
Chemical & Biopharmaceutical, Laboratories of Patras S.A. (Grèce)
Inventeur(s)
Barlos, Kleomenis K.
Barlos, Konstantinos
Gatos, Dimitrios
Ziovas, Michail
Liopyris, Efstathios
Abrégé
The present application discloses the preparation of peptides, including insulin and insulin derivatives, using efficient methods for solid-phase and solution phase peptide synthesis.
CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS S.A. (Grèce)
Inventeur(s)
Barlos, Kleomenis
Barlos, Konstantinos
Abrégé
The present invention relates to a process for preparing an epidermal growth factor-like peptide (EGF-like peptide) comprising the following amino acid sequence, C1(X)7C2(X)4-5C3(X)10-13C4(X)C5(X)8C6 [SEQ NO: 49] wherein C1-C6 are each cysteine and each X is independently a natural or unnatural amino acid, and wherein said EGF-like peptide has three intramolecular disulfide bonds; said process comprising the steps of: (I) preparing a first peptide fragment wherein the N-terminal amino acid is protected by a protecting group PG1, which is selected from Boo and Fmoc; (II) preparing a second peptide fragment wherein the C-terminal amino acid is protected by a protecting group PG2, which is selected from trityl, chlorotrityl and t-butyl; and wherein the amino acid side chains in said first and second peptide fragments are optionally protected; (III) coupling the C-terminal amino acid of said first peptide fragment with the N-terminal amino acid of said second peptide fragment in solution to form a linear protected EGF-like peptide; (IV)(a)(i) treating the linear protected EGF-like peptide formed in step (III) with iodine to form an oxidized mixture; (ii) globally deprotecting the oxidized mixture obtained in step (IV)(a)(i) by treating with trifluoroacetic acid (TFA); (iii) treating the deprotected oxidized mixture obtained in step (IV)(a)(ii) with DMSO/DTT to form a cmde EGF-like peptide; or (IV)(b)(i) globally deprotecting the linear protected EGF-like peptide obtained in step (III) by treating with trifluoroacetic acid (TFA); (ii) treating the deprotected mixture obtained in step (IV)(b)(i) with DMSO to form a cmde EGF-like peptide; and (V) optionally purifying the crude EGF-like peptide. Further aspects of the invention relate to processes for preparing EGF-like peptides using various fragment condensations.
CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS S.A. (Grèce)
Inventeur(s)
Barlos, Kleomenis
Gatos, Dimitrios
Barlos, Kostas K.
Vasileiou, Zoi
Abrégé
The present invention relates to peptide modifier compounds of Formula (1), or a salt thereof, wherein: a is an integer from 1 to 10, more preferably from 1 to 3; b is an integer from 0 to 7; Z is a terminal group and Y is a bivalent group. Further aspects of the invention relate to intermediates in the preparation of compounds of Formula (1), and the use of compounds of Formula (1) in the synthesis of peptide derivatives.
C07K 1/04 - Procédés généraux de préparation de peptides sur des supports
A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
C07C 269/04 - Préparation de dérivés d'acide carbamique, c.-à-d. de composés contenant l'un des groupes l'atome d'azote ne faisant pas partie de groupes nitro ou nitroso à partir d'amines avec formation de groupes carbamate
C07C 269/06 - Préparation de dérivés d'acide carbamique, c.-à-d. de composés contenant l'un des groupes l'atome d'azote ne faisant pas partie de groupes nitro ou nitroso par des réactions n'impliquant pas la formation de groupes carbamate
C07C 323/60 - Thiols, sulfures, hydropolysulfures ou polysulfures substitués par des halogènes, des atomes d'oxygène ou d'azote ou par des atomes de soufre ne faisant pas partie de groupes thio contenant des groupes thio et des groupes carboxyle liés au même squelette carboné ayant les atomes de soufre des groupes thio liés à des atomes de carbone acycliques du squelette carboné avec l'atome de carbone d'au moins un des groupes carboxyle lié à des atomes d'azote
C07K 1/107 - Procédés généraux de préparation de peptides par modification chimique de peptides précurseurs
C07K 14/00 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés
C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS S.A. (Grèce)
Inventeur(s)
Barlos, Kleomenis
Barlos, Konstantinos
Abrégé
The present invention relates to a process for preparing an epidermal growth factor-like peptide (EGF-like peptide) comprising the following amino acid sequence, C177C24-54-5C310-1310-13C4(X)C588C6[SEQ ID NO: 49] wherein C1-C6122, which is selected from trityl, chlorotrityl and t- butyl; and wherein the amino acid side chains in said first and second peptide fragments are optionally protected; (III) coupling the C-terminal amino acid of said first peptide fragment with the N- terminal amino acid of said second peptide fragment in solution to form a linear protected EGF-like peptide; (IV)(a) (i) treating the linear protected EGF-like peptide formed in step (III) with iodine to form an oxidized mixture; (ii) globally deprotecting the oxidized mixture obtained in step (IV)(a)(i) by treating with trifluoroacetic acid (TFA); (iii) treating the deprotected oxidized mixture obtained in step (IV)(a)(ii) with DMSO/DTT to form a crude EGF-like peptide; or (IV)(b) (i) globally deprotecting the linear protected EGF-like peptide obtained in step (III) by treating with trifluoroacetic acid (TFA); (ii) treating the deprotected mixture obtained in step (IV)(b)(i) with DMSO to form a crude EGF-like peptide; and (V) optionally purifying the crude EGF-like peptide. Further aspects of the invention relate to processes for preparing EGF-like peptides using various fragment condensations.
CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS S.A. (Grèce)
Inventeur(s)
Barlos, Kleomenis
Barlos, Konstantinos
Gatos, Dimitrios
Vasileiou, Zoi
Abrégé
A process for preparing a GLP-1 or GLP-2 peptide, said process comprising coupling in solution at least a first fragment and at least a second fragment, wherein the coupling comprises reacting the carboxy terminal amino acid of the first fragment with the amino terminal amino acid of the second fragment, and wherein the carboxy terminal amino acid of the first fragment is other than a Gly residue
CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRA (Grèce)
Inventeur(s)
Gatos, Dimitrios
Anastasiou, Alexandra
Barlos, Kleomenis
Abrégé
A-C-B (I)
q
n is 0, 1, 2 or 3.
Further aspects of the invention relate to pharmaceutical compositions comprising said polypeptide compound, and therapeutic uses thereof. Another aspect relates to the use of said polypeptide compounds in the preparation of insulin and derivatives thereof.
CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS S.A. (Grèce)
Inventeur(s)
Barlos, Kleomenis
Gatos, Dimitrios
Barlos, Kostas K.
Vasileiou, Zoi
Abrégé
The present invention relates to peptide modifier compounds of Formula (1), or a salt thereof, wherein: a is an integer from 1 to 10, more preferably from 1 to 3; b is an integer from 0 to 7; Z is a terminal group and Y is a bivalent group. Further aspects of the invention relate to intermediates in the preparation of compounds of Formula (1), and the use of compounds of Formula 1 in the synthesis of peptide derivatives.
A61K 47/54 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique
C07C 269/04 - Préparation de dérivés d'acide carbamique, c.-à-d. de composés contenant l'un des groupes l'atome d'azote ne faisant pas partie de groupes nitro ou nitroso à partir d'amines avec formation de groupes carbamate
C07C 269/06 - Préparation de dérivés d'acide carbamique, c.-à-d. de composés contenant l'un des groupes l'atome d'azote ne faisant pas partie de groupes nitro ou nitroso par des réactions n'impliquant pas la formation de groupes carbamate
C07C 323/60 - Thiols, sulfures, hydropolysulfures ou polysulfures substitués par des halogènes, des atomes d'oxygène ou d'azote ou par des atomes de soufre ne faisant pas partie de groupes thio contenant des groupes thio et des groupes carboxyle liés au même squelette carboné ayant les atomes de soufre des groupes thio liés à des atomes de carbone acycliques du squelette carboné avec l'atome de carbone d'au moins un des groupes carboxyle lié à des atomes d'azote
C07K 14/00 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés
C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
A61K 38/00 - Préparations médicinales contenant des peptides
CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS S.A. (Grèce)
Inventeur(s)
Barlos, Kleomenis
Barlos, Konstantinos
Gatos, Dimitrios
Vasileiou, Zoi
Abrégé
A process for preparing a GLP-1 or GLP-2 peptide, said process comprising coupling in solution at least a first fragment and at least a second fragment, wherein the coupling comprises reacting the carboxy terminal amino acid of the first fragment with the amino terminal amino acid of the second fragment, and wherein the carboxy terminal amino acid of the first fragment is other than a Gly residue
CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS S.A. (Grèce)
Inventeur(s)
Gatos, Dimitrios
Anastasiou, Alexandra
Barlos, Kleomenis
Abrégé
A first aspect of the invention relates to a polypeptide compound of formula (I): A-C-B (I) wherein: A is the A chain of insulin or a functional derivative or variant thereof; B is the B chain of insulin or a functional derivative or variant thereof; C is a peptide of the formula: (X1)p - (X2)n - (X3)q wherein: each X1 and X3 is independently a basic amino acid; each X2 is independently a natural or unnatural amino acid; p is 1 or 2; q is 0, 1 or 2: n is 0, 1, 2 or 3. Further aspects of the invention relate to pharmaceutical compositions comprising said polypeptide compound, and therapeutic uses thereof. Another aspect relates to the use of said polypeptide compounds in the preparation of insulin and derivatives thereof.
CHEMICAL & BIOPHARMACEUTICALS LABORATORIES OF PATRAS S.A. (Grèce)
Inventeur(s)
Barlos, Kleomenis
Gatos, Dimitrios
Barlos, Kostas
Ziovas, Michail
Abrégé
A first aspect of the invention relates to a single chain insulin analog comprising: (A) the A-chain of human or animal insulin, or an analog or derivative thereof; (B) the B-chain of human or animal insulin, or an analog or derivative thereof; (C) one or more disulfide bonds between said A-chain and said B-chain; and (D) a further covalent link, L, between a functional group of an amino acid in the A-chain and a functional group of an amino acid in the B-chain, at least one of said functional groups being an amino acid side chain functional group. Further aspects of the invention relate to pharmaceutical compositions comprising said single chain insulin derivatives, and therapeutic uses thereof.
CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS S.A. (Grèce)
Inventeur(s)
Barlos, Kleomenis K.
Abrégé
The present application discloses peptides and peptaibols of high purity may be obtained by solid phase peptide synthesis using as the starting resin hydroxy amino acids, hydroxy amino acid amides, hydroxy amino alcohols or small peptides containing hydroxy amino acids attached to polymers through their side chain.
CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS SA (Grèce)
Inventeur(s)
Barlos, Kleomenis
Barlos, Konstantinos
Abrégé
It is described the preparation of Insulin like peptides, of chimeric Insulin like peptides and of their derivatives by the random combination of their chains A and their chains B and the pharmaceutical application of the obtained products.
CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS S.A. (Grèce)
Inventeur(s)
Barlos, Kleomenis
Gatos, Dimitrios
Barlos, Kostas
Ziovas, Michail
Abrégé
A first aspect of the invention relates to a single chain insulin analogue comprising: (A) the A-chain of human or animal insulin, or an analogue or derivative thereof; (B) the B-chain of human or animal insulin, or an analogue or derivative thereof; (C) one or more disulfide bonds between said A-chain and said B-chain; and (D) a further covalent link, L, between a functional group of an amino acid in the A- chain and a functional group of an amino acid in the B-chain, at least one of said functional groups being an amino acid side chain functional group. Further aspects of the invention relate to pharmaceutical compositions comprising said single chain insulin derivatives, and therapeutic uses thereof.
A61K 47/48 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p.ex. supports, additifs inertes l'ingrédient non actif étant chimiquement lié à l'ingrédient actif, p.ex. conjugués polymère-médicament
CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS S.A. (Grèce)
Inventeur(s)
Barlos, Kleomenis
Gatos, Dimitrios
Barlos, Kostas, K
Vasileiou, Zoi
Abrégé
The present invention relates to peptide modifier compounds of Formula (1), or a salt thereof, wherein: a is an integer from 1 to 10, more preferably from 1 to 3; b is an integer from 0 to 7; Z is a terminal group and Y is a bivalent group. Further aspects of the invention relate to intermediates in the preparation of compounds of Formula (1), and the use of compounds of Formula 1 in the synthesis of peptide derivatives.
A61K 47/48 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p.ex. supports, additifs inertes l'ingrédient non actif étant chimiquement lié à l'ingrédient actif, p.ex. conjugués polymère-médicament
CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS S.A. (Grèce)
Inventeur(s)
Barlos, Kleomenis
Barlos, Kostas
Gatos, Dimitrios
Abrégé
The present invention relates to a peptide-resin conjugate of Formula (2), wherein: Pr1 is selected from H, alkyl, aryl, aralkyl, acyl, aroyl and a protecting group; Y is a direct bond; or an optionally protected natural or unnatural amino acid residue; or a peptide comprising 2 to 200 natural or unnatural amino acid residues, each of which is optionally protected; Dia is a natural or unnatural diamino acid; A is a polymer resin conjugated to the side chain amino function of the diamino acid; X is an optionally protected natural or unnatural amino acid residue; or a peptide comprising 2 to 15 natural or unnatural amino acid residues, each of which is optionally protected; R1, and R2 are each independently selected from H, alkyl, aryl, aralkyl, NH2, NH-CO-NH2. Further aspects of the invention relate to a process of preparing peptide-resin conjugates of Formula (2), and their use in the preparation of peptides.
CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS S.A. (Grèce)
Inventeur(s)
Barlos, Kleomenis K.
Abrégé
The present application discloses peptides and peptaibols of high purity may be obtained by solid phase peptide synthesis using as the starting resin hydroxy amino acids, hydroxy amino acid amides, hydroxy amino alcohols or small peptides containing hydroxy amino acids attached to polymers through their side chain.
CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS S.A. (Grèce)
Inventeur(s)
Barlos, Kleomenis K.
Abrégé
The present application discloses peptides and peptaibols of high purity may be obtained by solid phase peptide synthesis using as the starting resin hydroxy amino acids, hydroxy amino acid amides, hydroxy amino alcohols or small peptides containing hydroxy amino acids attached to polymers through their side chain.
C07K 14/435 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains
CHEMICAL & BIOPHARMACEUTICAL LABORATORIES, OF PATRAS SA (Grèce)
Inventeur(s)
Barlos, Kleomenis
Barlos, Konstantinos
Abrégé
It is described the preparation of Insulin like peptides, of chimeric Insulin like peptides and of their derivatives by the random combination of their chains A and their chains B and the pharmaceutical application of the obtained products.
CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS S.A. (Grèce)
Inventeur(s)
Barlos, Kleomenis, K.
Abrégé
A process for producing an insulin type peptide, for example a relaxin, involving oxidizing a methionine residue on a B-chain having cysteine residues and combining the B chain with an A chain having cysteine residues to form a peptide having intermolecular disulphide links and biological activity. Novel synthetic relaxin 1 and methionine oxidized relaxins and Met(O) B-chains having enhanced solubility are disclosed.
brevets
