Process for the preparation of c-terminally amidated peptides

C - Chemistry – Metallurgy – 12 – P

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C12P 21/00 (2006.01) C07K 1/00 (2006.01) C12N 9/48 (2006.01) C12P 21/02 (2006.01)

Patent

CA 2092721

Preparation of C-terminally amidated peptides P-NH2 by reacting a substrate component selected from a) C-terminally unblocked peptides P-OH,b) peptides or peptide derivatives P-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 P- OR', where R' is alkyl, aryl, heteroaryl, ar- alkyl or an .alpha.-des amino fragment of an amino acid; with a nucleophile component in the present of an enzyme using as nuclo- phile a compound NH2-R capable of cleaving the reaction product P-NH-R to P- NH2, and undertaking such cleavage. Pre- ferred nucleophiles are selected from (I), wherein A-F and A'-E' are carbon atoms or up to two hetero atoms, Y is H, alkyl, aryl; aralkyl,oxo or carboxy, or a functional derivative thereof, X1-X5 are H or various substituents. The cleavage may be induced by photolysis, solvolysis, reduction, rearrangement elimination or oxidation. The process is very flexible in that it may be adapted to any type of enzymatic synthesis and lend itself to C- terminal amidation of all types of peptides.

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