| 摘要 |
The present invention provides a method for acylating one or more amino groups (typically arising from lysine) of a peptide (or protein), e.g. GLP-1, the method comprising (a) reacting a peptide (or protein) having at least one free amino group with an acylating agent of general formula (I) wherein n is 0-8; R<1> is COOR<4>; R<2> is a lipophilic moiety, e.g. selected from C3-39-alkyl, C3-39-alkenyl, C3-39-alkadienyl and steroidal residues; R<3> together with the carboxyl group to which R<3> is attached designa te a reactive ester or a reactive N-hydroxy imide ester; and R<4> is selected from hydrogen, C1-12-alkyl and benzyl,under basic conditions in a mixture of an aprotic polar solvent and water (e.g. N-methyl-2-pyrrolidone and water); and (b) if R<4> is not hydrogen, saponifying the acylated peptide ester group (COOR<4>) under basic conditions (e.g. at a pH in the range of 7-14); in order to obtain an N-acylated peptide (or an N-acylated protein). |
