Process for the preparation of C-terminally amidated peptides

Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Enzymatic production of a protein or polypeptide

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435212, 435213, C12P 2106, C12N 948, C12N 976

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active

055807518

ABSTRACT:
A process for preparing C-terminally amidated peptides, Peptide-NH.sub.2, is presented. In a first step, a substrate component is reacted with a nucleophile component in the presence of trypsin or a carboxypeptidase using as nucleophile a compound NH.sub.2 -R to form a first reaction product Peptide-NH-R. In a second step, the first reaction product is non-enzymatically chemically cleaved to form the C-terminally amidated product, Peptide-NH.sub.2. The substrate component is selected from a) peptide derivatives Peptide-X-Y, where X is an amino acid or peptide residue and Y is OH, OMe or C-terminal modification and c) C-terminally esterified peptides, Peptide-OR', where R' is alkyl, aryl, heteroaryl, or aralkyl. The nucleophile component is selected from ##STR1## wherein A-F and A'-E' are carbon atoms or up to two hetero atoms, Y is H, alkyl, aryl, aralkyl, oxo or carboxy, X.sup.1 -X.sup.5 are H or various substituents. The cleavage may be induced by photolysis, solvolysis, reduction, rearrangement elimination, or oxidation. The process may be adapted to enzymatic synthesis and lends itself to C-terminal amidation of many types of peptides.

REFERENCES:
patent: 4018790 (1977-04-01), Paget et al.
patent: 4062746 (1977-12-01), Rich et al.
patent: 4511505 (1985-04-01), Morihara et al.
patent: 4708934 (1987-11-01), Gilligan et al.
patent: 4709014 (1987-11-01), Tamaoki
patent: 4806473 (1989-02-01), Johansen et al.
patent: 4806534 (1989-02-01), Leonardi et al.
patent: 4921797 (1990-05-01), Matsuo et al.
patent: 5190875 (1993-03-01), Steinke et al.
Rich et al., "Removal of C-Terminal peptide Amides from a 3-Nitro-4-Aminomethyl-Benzyl Amide Resin by Photolysis," Tetrahedron Lett., 5:301-304 (1975).
S. Wang, "Solid Phase Synthesis of Protected Peptides via Photolytic Cleavage of the .alpha.-Methylphenacyl Ester Anchoring Linkage," J. Org. Chem., 41:3258-3261 (1976).
F. Widmer et al., "Influence of the Structure of Amine Components on Carboxypeptidase Y Catalyzed Amide Bond Formation," Carlsberg Res. Commun., 46:97-106 (1981).
K. Breddam, "Enzymatic Properties of Malt Carboxypeptidase II in Hydrolysis and Aminolysis Reactions" Carlsberg Res. Commun., 50:309-323 (1985).
K. Breddam et al., "Primary Structure and Enzymatic Properties of Carboxypeptidase II from Wheat Bran," Carlsberg Res. Commun., 52:297-311 (1987).
K. Breddam, "Carboxypeptidases S-1 from Penicillium Janthinellum: Enzymatic Properties in Hydrolysis and Aminolysis Reactions," Carlsberg Res. Commun., 53:309-320 (1988).
J. Johansen et al., "Isolation of Carboxypeptidase Y by Affinity Chromatography," Carlsberg Res. Commun., 41:1-14 (1976).
Y. Kubota et al., "Carboxypeptidase C.sub.n," J. Biochem., 74:757-770 (1973).
B. Penke et al., "Solid-Phase Synthesis of Peptide Amides on a Polystyrene Support Using Fluorenylmethoxycarbonyl Protecting Groups," J. Org. Chem, 52:1197-1200 (1987).
V. Pillai et al., "3 Nitro-4-Aminomethyl Benzoyl Derivatives of Poly Ethylene Glycols: a New Class of Photosensitive Soluble Polymer Carriers for the Synthesis of Carboxy Terminal Peptide Amides," Tetrahedron Lett., 36:3409-3412 (1979). English Abstract--Chem. Abstracts 93:740 (1908), Abst. No. 26764X.
V. Pillai et al., "New Easily Removable Poly(ethylene glycol) Supports for the Liquid-Phase Method of Peptide Synthesis," J. Org. Chem., 45:5364-5370 (1980).
A. Ajayaghosh et al., "Solid-Phase Synthesis of N-methyl--and N-Ethylamides of Peptides Using Photolytically Detachable ((3-nitro-4-((alkylamino)methyl)benzamido)methyl)-polystyrene Resin," J. Org. Chem., 55:2826-2829 (1990).
K. Breddam et al., "Carboxypeptidase Y Catalyzed Transpeptidations and Enzymatic Peptide Synthesis," Carlsberg Res. Commun., 45:237-247 (1980).
K. Breddam et al., "Carboxypeptidase Y Catalyzed C-Terminal Modifications of Peptides," Carlsberg Res. Commun., 46:121-128 (1981).
K. Breddam et al., "Carboxypeptidase Y Catalyzed C-Terminal Modification in the B-Cahin of Procine Insulin," Carlsberg Res. Commun., 46:361-372 (1981).
K. Breddam et al., "Isolation of Carboxypeptidase from Malted Barley by Affinity Chromatography," Carlsberg Res. Commun., 48:217-230 (1983).
K. Breddham et al., "Carboxypeptidase Y Catalyzed Transpeptidation and Condensation Reactions," Carlsberg Res. Commun., 49:457-462 (1984).
K. Breddam et al., "Malt Carboxypeptidase Catalyzed Aminolysis Reactions", Carlsberg Res. Commun., 49:473-481 (1984).
K. Breddam, "Isolation of Carboxypeptidase II from Malted Barley by Affinity Chromatography," Carlsberg Res. Commun., 50:199-209 (1985).
Breddam, "Serine Carboxypeptidases. A Review", Carlsberg. Res. Commun., 51, 83-128 (1986).

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