WO1992022566A1 - Geschützter aminosäurebaustein, herstellung und verwendung - Google Patents

Geschützter aminosäurebaustein, herstellung und verwendung Download PDF

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Publication number
WO1992022566A1
WO1992022566A1 PCT/EP1992/001280 EP9201280W WO9222566A1 WO 1992022566 A1 WO1992022566 A1 WO 1992022566A1 EP 9201280 W EP9201280 W EP 9201280W WO 9222566 A1 WO9222566 A1 WO 9222566A1
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WO
WIPO (PCT)
Prior art keywords
amino acid
building block
amino
group
protected
Prior art date
Application number
PCT/EP1992/001280
Other languages
German (de)
English (en)
French (fr)
Inventor
Ralf Bartl
Ronald Frank
Original Assignee
GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF)
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 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) filed Critical GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF)
Priority to JP51124692A priority Critical patent/JP3296434B2/ja
Priority to EP92911418A priority patent/EP0589927A1/de
Publication of WO1992022566A1 publication Critical patent/WO1992022566A1/de

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
    • 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
    • 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

Definitions

  • oligo- and polypeptides have become an important tool. They are used for the production of specific antibodies for immunoaffinity chromatography, identification of unknown gene products and the development of vaccines against pathogens, as peptide hormones and their analogs with agonistic or antagonistic activity, as model compounds in protein structure studies and many others.
  • peptides are oligomers or polymers (n to about 150) of amino acids linked via amide bonds (peptide bonds).
  • peptides are also understood to mean those which, in addition to the 20 natural L- ⁇ -amino acids, also contain non- ⁇ -, D- or chemically modified amino acids (any R).
  • the chemical synthesis of the peptides is carried out in stages
  • Carrier loads were also tested for various additives such as salts or urea during synthesis (e.g. F.C. Westall, A.
  • the object on which the invention is based is achieved by an amino acid building block for peptide synthesis, in which a hydrogen atom of the amino group to be incorporated into a peptide bond is protected by a temporary amino protecting group which can be split off under non-acidic conditions, this building block being characterized in this way is
  • Dipeptide building block acts, the hydrogen atom of the peptide bond can also be protected by such a further protective group, or
  • the oligopeptide building block acts, even one or all of the hydrogen atoms of the peptide bonds can be protected by such a further protective group.
  • the amino acid building block according to the invention can be a building block for a single amino acid, a dipeptide building block or an oligopeptide building block.
  • the amino group to be bound to a peptide bond can be an ⁇ or ⁇ -terminal amino group.
  • the temporary amino protecting group can be a
  • Act urethane group for example fluorenylmethoxycarbonyl (Fmoc).
  • the carboxyl group of the amino acid building block can be free, also protected or activated (active ester).
  • the amino acid building block according to the invention can be characterized by a further protective group (R '''- X-CH 2 -), which can be found under
  • the invention relates to a method for producing an amino acid building block for peptide synthesis, which is characterized in that one starts from a conventional amino acid building block in which a hydrogen atom of the amino group to be bound by a peptide bond is protected by a temporary amino protective group which is protected under non- acidic conditions, and the other hydrogen atom is free, and this usual amino acid building block of a Mannich reaction using an H-acidic compound (R '' '- XH), in which the acidic H atom with a heteroatom ( X) is linked to a lone pair of electrons, for example using an alcohol, a thioalcohol or a secondary amine.
  • amino acid building blocks according to the invention can be used for the amino acid building blocks according to the invention.
  • amino acid building block For the production of the amino acid building block according to the invention one can start from a common amino acid building block of the following general formula:
  • R-CO ⁇ -amino protecting group according to the state of the art, which can be split off under non-acidic conditions
  • R ' side chain of the AS
  • R " OH, active ester or protective group
  • R"' rest of the new protective group
  • X O, S, NR N (R N ⁇ H) etc.
  • Such a Mannich reaction can also be carried out with a fully protected di- or oligopeptide.
  • the new protective group is introduced both at the N-terminus and at the medium peptide bonds. This would convert an oligopepud fragment that was insoluble in the solvent used for peptide synthesis into a soluble form. The cleavage takes place as a reverse reaction.
  • the new amino acid was obtained as a rotation-inhibited conformer mixture of the CO-N bond (signal doubling in the NMR spectrum), but this is not important for peptide synthesis.
  • Fmoc-Gly-OH is advantageous as a lithium salt for the above. Regulation used. Fmoc- (Mom) Gly-OLi is obtained almost quantitatively.
  • the Fmoc-protected dipeptide is treated with approx. 300 ⁇ l 20% piperidine / DMF for 20 min and, after removing the solvent in vacuo, w. o. separated chromatographically
  • the (Ala) 13 was synthesized on cellulose disks with acid-labile benzyl linker (R. Frank, R. Döring, Tetrahedron, 44, 6031 (1988)), which were already loaded with Fmoc-Ala-OH. The remaining AS were coupled in 20 mM amino acid solution with about 4-fold excess for filter loading in DMF.
  • the final cleavage of the peptide was carried out with 95% TFA, 3% cysteine, 2% H 2 O.
  • the lyophilized product was then separated by HPLC and detected by FAB-MS.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biophysics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Peptides Or Proteins (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
PCT/EP1992/001280 1991-06-13 1992-06-05 Geschützter aminosäurebaustein, herstellung und verwendung WO1992022566A1 (de)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP51124692A JP3296434B2 (ja) 1991-06-13 1992-06-05 保護されたアミノ酸構成単位、生産と使用
EP92911418A EP0589927A1 (de) 1991-06-13 1992-06-05 Geschützter aminosäurebaustein, herstellung und verwendung

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DEP4119544.2 1991-06-13
DE19914119544 DE4119544C1 (enrdf_load_stackoverflow) 1991-06-13 1991-06-13

Publications (1)

Publication Number Publication Date
WO1992022566A1 true WO1992022566A1 (de) 1992-12-23

Family

ID=6433885

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1992/001280 WO1992022566A1 (de) 1991-06-13 1992-06-05 Geschützter aminosäurebaustein, herstellung und verwendung

Country Status (4)

Country Link
EP (1) EP0589927A1 (enrdf_load_stackoverflow)
JP (1) JP3296434B2 (enrdf_load_stackoverflow)
DE (1) DE4119544C1 (enrdf_load_stackoverflow)
WO (1) WO1992022566A1 (enrdf_load_stackoverflow)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996007671A1 (de) * 1994-09-03 1996-03-14 Ernst Bayer Racemisierungsfreie herstellung von n-aminosäure-derivaten und dipeptiden
US5770687A (en) * 1995-06-07 1998-06-23 Peptor Limited Comformationally constrained backbone cyclized somatostatin analogs
US5811392A (en) * 1994-06-08 1998-09-22 Yissum Research Development Co. Of The Hebrew University Conformationally constrained backbone cyclized peptide analogs
US6051554A (en) * 1995-06-07 2000-04-18 Peptor Limited Conformationally constrained backbone cyclized somatostatin analogs
US6117974A (en) * 1991-10-02 2000-09-12 Peptor Limited Libraries of backbone-cyclized peptidomimetics
AU724386B2 (en) * 1994-06-08 2000-09-21 Peptor Ltd Conformationally constrained backbone cyclized peptide analogs
US6355613B1 (en) 1996-07-31 2002-03-12 Peptor Limited Conformationally constrained backbone cyclized somatostatin analogs
US6841533B1 (en) 1995-12-07 2005-01-11 Peptor Limited Conformationally constrained backbone cyclized interleukin-6 antagonists
US7084244B2 (en) 1994-06-08 2006-08-01 Develogen Israel Ltd. Conformationally constrained backbone cyclized peptide analogs

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103025165B (zh) * 2010-05-05 2016-06-08 普罗林科斯有限责任公司 自大分子共轭物的控释
WO2023219152A1 (ja) * 2022-05-13 2023-11-16 中外製薬株式会社 リチウム塩の析出工程を含む、アミノ酸の塩若しくはペプチド化合物の塩又はこれらの溶媒和物の製造方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH516523A (fr) * 1969-11-25 1971-12-15 Sogespar S A Procédé de préparation des dérivés des acides a-aminés N-disubstitués par benzoylation

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH516523A (fr) * 1969-11-25 1971-12-15 Sogespar S A Procédé de préparation des dérivés des acides a-aminés N-disubstitués par benzoylation

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
CHEMISTRY LETTERS. Nr. 11, November 1989, TOKYO JP Seiten 1963 - 1966; T SHONO ET AL.: 'a new facile method for construction of beta-arylpyrrolidine rings and its application to synthesis of racemic mesembrine' *
CHEMISTRY LETTERS. Nr. 8, August 1981, TOKYO JP Seiten 1121 - 1124; T SHONO ET AL.: 'one step synthesis of alpha-aminoalkylfurans and its application to a facile synthesis of pyridoxine (vitamine b6)' *
PEPTIDES: CHEMISTRY AND BIOLOGY (J A SMITH AND J E RIVIER, EDS). PROCEEDINGS OF THE XII AMERICAN PEPTIDE SYMPOSIUM, CAMBRIDGE, JUNE 16-21, 1991 ESCOM, LEIDEN Seiten 505 - 506; R BARTL ET AL.: 'towards elimination of segmenzt insolubility during SPPS' *
TETRAHEDRON LETTERS. Bd. 22, Nr. 34, 1981, OXFORD GB Seiten 3249 - 3252; T SHONO ET AL.: 'a new carbon-phosphorus bond forming reaction and synthesis of aminoalkylphosphonic acid derivatives' *
TETRAHEDRON LETTERS. Nr. 9, 1977, OXFORD GB Seiten 749 - 750; D H RICH AND J P TAM: 'a method for introducing secondary amide bonds into strained cyclic peptides' *

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6117974A (en) * 1991-10-02 2000-09-12 Peptor Limited Libraries of backbone-cyclized peptidomimetics
AU724386B2 (en) * 1994-06-08 2000-09-21 Peptor Ltd Conformationally constrained backbone cyclized peptide analogs
US5811392A (en) * 1994-06-08 1998-09-22 Yissum Research Development Co. Of The Hebrew University Conformationally constrained backbone cyclized peptide analogs
US5883293A (en) * 1994-06-08 1999-03-16 Peptor Ltd. Conformationally constrained backbone cyclized peptide analogs
US6265375B1 (en) 1994-06-08 2001-07-24 Yissum Research Development Co. Of The Hebrew University Conformationally constrained backbone cyclized peptide analogs
US7084244B2 (en) 1994-06-08 2006-08-01 Develogen Israel Ltd. Conformationally constrained backbone cyclized peptide analogs
WO1996007671A1 (de) * 1994-09-03 1996-03-14 Ernst Bayer Racemisierungsfreie herstellung von n-aminosäure-derivaten und dipeptiden
US6051554A (en) * 1995-06-07 2000-04-18 Peptor Limited Conformationally constrained backbone cyclized somatostatin analogs
US5770687A (en) * 1995-06-07 1998-06-23 Peptor Limited Comformationally constrained backbone cyclized somatostatin analogs
US6841533B1 (en) 1995-12-07 2005-01-11 Peptor Limited Conformationally constrained backbone cyclized interleukin-6 antagonists
US6355613B1 (en) 1996-07-31 2002-03-12 Peptor Limited Conformationally constrained backbone cyclized somatostatin analogs
US6930088B2 (en) 1998-06-19 2005-08-16 Peptor Ltd. Conformationally constrained backbone cyclized somatostatin analogs
US7060679B2 (en) 1998-06-19 2006-06-13 Develogen Israel Ltd. Conformationally constrained backbone cyclized somatostatin analogs

Also Published As

Publication number Publication date
JPH07501312A (ja) 1995-02-09
JP3296434B2 (ja) 2002-07-02
DE4119544C1 (enrdf_load_stackoverflow) 1992-10-15
EP0589927A1 (de) 1994-04-06

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