| 摘要 |
<p>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; R1 is COOR4; R2 is a lipophilic moiety, e.g. selected from C¿3-39?-alkyl, C3-39-alkenyl, C3-39-alkadienyl and steroidal residues; R?3¿ together with the carboxyl group to which R3 is attached designa te a reactive ester or a reactive N-hydroxy imide ester; and R4 is selected from hydrogen, C¿1-12?-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 (COOR4) 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).</p> |
