| 摘要 |
A process for enzymatic replacement of the B-30 amino acid in insulins, in which the insulin Ins-X, wherein Ins represents the insulin molecule except for X which represents the B-30 amino acid, is reacted with an amine component selected from amino acids, and their amides and esters, of the formulae… H-B-OH… H-B-NR<1>R<2>… H-O-OR<3>… H-B-SR<3>… H-B-SeR<3>… wherein B is an amino acid residue; either R<1> and R<2> are independently selected from hydrogen, amino, hydroxy, alkyl, cycloalkyl, aryl, heteroaryl and aralkyl or NR<1>R<2> is a heterocyclic group which may contain a further hetero atom; and R<3> is alkyl, cycloalkyl, aryl, heteroaryl or aralkyl; in the presence of an L-specific serine or thiol carboxy-peptidase enzyme, in an aqueous solution or dispersion having a pH from about 7 to 10.5, to form an insulin derivative of the formulae… Ins-B-OH, Ins-B-NR<1>R<2>, Ins-B-B-NR<1>R<2>… Ins-B-OR<3>, Ins-B-SR<3> or Ins-B-SeR<3>… wherein Ins, B, R<1>, R<2> and R<3> are as defined above; and, if desired, cleaving any -NR<1>R<2>, -B-NR<1>R<2>, -OR<3>, -SR<3> or -SeR<3> group. The invention allows human insulin to be prepared from porcine insulin and threonine. |
