[go: up one dir, main page]

EP3713951A1 - Procédé de préparation de peptides - Google Patents

Procédé de préparation de peptides

Info

Publication number
EP3713951A1
EP3713951A1 EP18807999.0A EP18807999A EP3713951A1 EP 3713951 A1 EP3713951 A1 EP 3713951A1 EP 18807999 A EP18807999 A EP 18807999A EP 3713951 A1 EP3713951 A1 EP 3713951A1
Authority
EP
European Patent Office
Prior art keywords
peptide
group
amino acid
water
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.)
Pending
Application number
EP18807999.0A
Other languages
German (de)
English (en)
Inventor
Sascha KNAUER
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.)
Sulfotools GmbH
Original Assignee
Sulfotools GmbH
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 Sulfotools GmbH filed Critical Sulfotools GmbH
Publication of EP3713951A1 publication Critical patent/EP3713951A1/fr
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/06—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents
    • C07K1/061—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents using protecting groups
    • C07K1/063—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents using protecting groups for alpha-amino functions
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
    • C07K1/042—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers characterised by the nature of the carrier
    • 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
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Definitions

  • the present invention relates to a method for preparing peptides, and to peptides being obtainable by the method.
  • said solid phase is an ion exchanger and said forming of a peptide bond is achieved while an amino acid or a peptide is ionically bound to the ion exchanger.
  • the ionically bounding to the ion exchanger may include any step of forming the peptide bond comprising the activation of the carboxyl group of an amino acid or peptide, the reaction of the activated carboxyl group of an amino acid or peptide with an amino group of another amino acid or another peptide or both steps.
  • the present invention can be achieved using a protic solvent, such as water, primary, secondary and/or tertiary alcohols.
  • a protic solvent such as water, primary, secondary and/or tertiary alcohols.
  • Primary and secondary amines should not be used as a solvent based on the coupling reaction for forming a peptide bond.
  • the synthesis of a peptide is build up via the carboxyl group of an amino acid or peptide and a carboxyl group of the second amino acid or second peptide being reacted with said first activated amino acid or first peptide is not protected
  • the method comprises the steps of activating a first amino acid or first peptide, removing an excess of coupling agent, adding a second amino acid or second peptide to the first activated amino acid or first peptide and reacting the second amino acid or second peptide with the first activated amino acid or first peptide and forming a peptide bond, removing residues of the reaction by a washing step. These steps can be repeated in order to achieve a desired peptide.
  • the coupling agent is a combination of a carbodiimide, preferably diisopropylcarbodiimide (DIC), dicyclohexylcarbodiimid (DCC), 1 -ethyl-3-(3- dimethylaminopropyl)carbodiimid (EDC), 2-(((ethylimino)methylene)amino)-2- methylpropane-1 -sulfonate (ESC) and 2,2'-(methanediylidenebis(azanylylidene)) bis(2-methylpropane-1 -sulfonate) (DSC), and an active ester forming compound, preferably 1 -hydroxybenzotriazole (HOBt), 1 -hydroxy-7-azabenzotriazole (HOAt), N-hydroxysuccinimide (NHS), ethylcyano(hydroxyimino)acetate (Oxyma), hydroxy- 3, 4-dihydro-4-oxo
  • the protective agent comprises water- solubility enhancing functional groups that are all of the same kind, in particular, all of the kind SO3 .
  • the protective agent comprises water- solubility enhancing functional groups of different kinds.
  • the water- solubility enhancing functional group is SO3
  • Preferred protective agents having the 9-methylfluorene backbone structure of the present invention can be illustrated by the following general formula 1 :
  • R3 is selected from SO3 , PO3 2 , N(CH3)2, N(CH3)3 + , OSO3 ester, OPO3 2 ester and CN, in particular R3 is SO3 .
  • R1 , R2, R4 and R5 are hydrogen.
  • R3, R8 and R13 are selected from SO3 , OSO3 ester, OPO3 2 ester, PO3 2 , N(CH3)2, N(CH3)3 + and CN, in particular R3, R8 and R13 are SO3 .
  • R1 , R2, R4 to R7, R9 to R12, R14 and R15 are hydrogen.
  • R2 and R6 are selected from SO3 , PO3 2 , OSO3 ester, OPO3 2 ester, N(CH3)2, N(CH3)3 + and CN, in particular R2 and R6 are SO3 .
  • R3 is selected from SO3 , PO3 2 , OSO3 ester, OPO3 2 ester, N(CH3)2, N(CH3)3 + and CN, in particular R3 is SO3 .
  • R1 , R2, R4 and R5 are hydrogen.
  • Preferred thiol protecting groups are shown in the following formulae 20 and 21.
  • the sulfur shown in the following general formula belongs to the protected thiol group:
  • R1 to R5 that are not SO3 ⁇ , OSO3 ⁇ ester, OPO3 2 ⁇ ester, PO3 2 ⁇ , N(CH3)2, N(CH3)3 + or CN are hydrogen.
  • said side chain protecting group comprises at least one water-solubility enhancing functional group, preferably ionic group.
  • forming of the peptide bond is preferably achieved at a temperature in the range of -20 to 100 °C, more preferably 0 to 50 °C, even more preferably 10 to 30 °C.
  • the releasing composition is preferably a composition deprotecting the peptide from the corresponding protecting group or a composition being able to release the peptide from the ion exchanger and maintaining the protection of the peptide.
  • the deprotecting agent being used for releasing the peptide from the solid support depends on the protecting group being used.
  • a Sboc group is conventionally released by an acidic composition while basic reagents are used to remove the Smoc moiety.
  • the ion exchanger is regenerated with 1 M NaCI solution and washed twice with water.
  • Smoc-lle-OH is added to the ion exchange resin at a maximum load and is activated by 3 equivalents 1 -ethyl-3-(3-dimethylaminopropyl)carbodiimid (EDO) and 2 equivalents N-hydroxysuccinimide (NHS) in mixture of water and acetonitrile (MeCN) 3:1 ratio (volume).
  • EEO 1 -ethyl-3-(3-dimethylaminopropyl)carbodiimid
  • NHS N-hydroxysuccinimide
  • the ion exchanger loaded with the activated Smoc-Leu is washed twice with water.
  • Val solved in water 1.5 equivalents Val solved in water are added to the activated Smoc-LAG and reacted at 25°C for 15 minutes at pH 7 under agitation. Excess of Val and released NHS are removed by washing with water.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Analytical Chemistry (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne un procédé de préparation de peptides comprenant une étape consistant à former une liaison peptidique, au moins un acide aminé ou un peptide comprenant un groupe protecteur ayant un groupe améliorant l'hydrosolubilité, et ladite formation de liaison peptidique étant obtenue par la liaison d'un acide aminé ou d'un peptide à une phase solide. L'invention concerne également des peptides comprenant un groupe protecteur ayant un groupe améliorant l'hydrosolubilité lié au groupe amino et un groupe carboxyle activé ou libre.
EP18807999.0A 2017-11-24 2018-11-23 Procédé de préparation de peptides Pending EP3713951A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102017127836 2017-11-24
PCT/EP2018/082404 WO2019101940A1 (fr) 2017-11-24 2018-11-23 Procédé de préparation de peptides

Publications (1)

Publication Number Publication Date
EP3713951A1 true EP3713951A1 (fr) 2020-09-30

Family

ID=64457019

Family Applications (1)

Application Number Title Priority Date Filing Date
EP18807999.0A Pending EP3713951A1 (fr) 2017-11-24 2018-11-23 Procédé de préparation de peptides

Country Status (2)

Country Link
EP (1) EP3713951A1 (fr)
WO (1) WO2019101940A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024143052A1 (fr) * 2022-12-26 2024-07-04 学校法人神戸学院 Procédé de synthèse de peptide
CN120737012B (zh) * 2025-08-29 2025-11-18 苏州金顶生物有限公司 一种新型保护氨基酸、制备方法及其应用

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BR9906091A (pt) * 1999-12-22 2002-06-04 Conselho Nacional Cnpq Usos de resina de troca aniÈnica (epm-7) como suporte sólido para a sìntese peptìdica e para cromatografia de afinidade
WO2013115813A1 (fr) 2012-02-01 2013-08-08 Cem Corporation Synthèse de peptide en phase solide, soluble dans l'eau
JP6736546B2 (ja) 2014-09-29 2020-08-05 サルフォトゥールズ ゲーエムベーハー ペプチドを合成する方法およびペプチドを固相合成する方法を実施するための装置

Also Published As

Publication number Publication date
WO2019101940A1 (fr) 2019-05-31

Similar Documents

Publication Publication Date Title
US11976094B2 (en) Method for preparing peptides
EP1115739B1 (fr) Auxiliaire pour la formation de liaisons amides
AU2022332278B2 (en) Compounds and methods for liquid phase synthesis
EP2215106B1 (fr) Support solide à greffe indole pour synthèse peptidique en phase solide fmoc
RU2727200C2 (ru) Способ пептидного синтеза и устройство для осуществления способа твердофазного пептидного синтеза
WO2019101940A1 (fr) Procédé de préparation de peptides
US20250333436A1 (en) Aqueous Solid Phase Peptide Synthesis
IE67453B1 (en) Process for the solubilization of peptides and process for peptide synthesis
WO2020144111A1 (fr) Purification exempte de hplc de peptides par l'utilisation de nouveaux réactifs de coiffage et de capture
WO2023033017A1 (fr) Procédé pour la production de ganirélix ou d'un sel de celui-ci
CN115181158A (zh) Fmoc基团裂解方法
WO2021144388A1 (fr) Procédé de synthèse du nangibotide
AU768649B2 (en) Auxiliary for amide bond formation
JP5670332B2 (ja) ピペコリン酸リンカーおよび固体支持体についての化学へのその使用
HK1190728A (en) A process for extraction of peptides and its application in liquid phase peptide synthesis
TW201307379A (zh) 萃取胜肽之方法及其於液相胜肽合成之應用

Legal Events

Date Code Title Description
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: UNKNOWN

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

Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE

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

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

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20200616

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME

DAV Request for validation of the european patent (deleted)
DAX Request for extension of the european patent (deleted)