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)
• 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)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

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Cited By (9)

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Citations (1)

• 1991
  • 1991-06-13 DE DE19914119544 patent/DE4119544C1/de not_active Expired - Fee Related
• 1992
  • 1992-06-05 EP EP92911418A patent/EP0589927A1/de not_active Withdrawn
  • 1992-06-05 WO PCT/EP1992/001280 patent/WO1992022566A1/de not_active Application Discontinuation
  • 1992-06-05 JP JP51124692A patent/JP3296434B2/ja not_active Expired - Fee Related

Patent Citations (1)

Non-Patent Citations (5)

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