Method for producing acylated peptides

摘要

The present invention provides a method for acylating one or more amino groups of a peptide where the acylation reaction is to be performed in an aqueous mixture containing less than 10% w/w aprotic polar solvent.

主权项

1. A method for producing an N-acylated peptide, said method comprising:
a) reacting a peptide having at least one free amino group with an acylating agent of the general formula I wherein
n is 0-8;R1 is COOR4;R2 is selected from C3-39-alkyl, C3-39-alkenyl, C3-39-alkadienyl and steroidal residues;R3 together with the carboxyl group to which R3 is attached designate a reactive ester or a reactive N-hydroxy imide ester; andR4 is selected from hydrogen; wherein said peptide is Arg34Lys26(N∈-(γ-Glu(Nα-hexadecanoyl)))-GLP-1(7-37); wherein the acylating agent is in an aqueous mixture under basic conditions containing 7% w/w or less aprotic polar solvent stabilized with an acid; and wherein said N-acylated peptide contains no more than 2% of the closely-related impurity Arg34Lys26-[N-∈-(α-Glu(N-hexadecanoyl))]-GLP-17-37 as determined by RP-HPLC.