Process for the c-terminal modification of peptides having a...

C - Chemistry – Metallurgy – 12 – P

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C12P 21/02 (2006.01) C07K 14/585 (2006.01) C12N 9/02 (2006.01)

Patent

CA 2101074

2101074 9215695 PCTABS00016 C-terminally modified peptides of the formula Peptide - Pro - NH-R, wherein R is selected from hydrogen, hydroxy, C1-6 alkyl, hydroxy C1-6 alkyl and C6-9 aralkyl or R is NHR1 wherein R1 is hydrogen C1-6 alkyl, C6-9 aralkyl or a group CO-R2, wherein R2 is selected from NH2, C1-6 alkyl and C6-9 aralkyl, e.g. calcitonin, are prepared by reacting a substrate component of the formula Peptide - Pro - X, wherein X is an amino acid having a side chain comprising at least two carbon atoms and further comprising at least one hetero atom selected from N, O and S, with a nucleophile component NH2-R, wherein R has the above meaning in the presence of an L-specific serine or thiolcarboxypeptidase enzyme from yeast or of animal, vegetable or other microbial origin, preferably carboxypeptidase Y from yeast, in an aqueous solution or dispersion having a pH of from 7.5 to 10 and optionally containing up to 25 % of an organic solvent. X is preferably selected from Met, Thr, Tyr, Met(o), His, Gln, Asn, Arg, Lys and Trp. Human calcitonin(1-32)Met-OH is a useful intermediate. The process enables a selective C-terminal amidation of peptides in good yields.

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