| 摘要 |
<p>The B-30 amino acid in insulins is replaced enzymatically by
reacting as substrate component the selected insulin Ins-X, wherein X represents the B-30 amino acid
with an amine component selected from the group consisting of
(a) L-amino acids of the formula
H - B - OH
wherein B is an L-amino acid residue,
(b) optionally N-substituted L-amino acid amides of the formula
H - B - NR<1>R<2>
wherein B is an L-amino acid residue and R<1> and R<2> are independently selected from the group consisting of hydrogen, amino, hydroxy, alkyl, cycloalkyl, aryl, heteroaryl and aralkyl or R<1> and R<2> together with the nitrogen atom form a heterocyclic group which may contain a furter hetero atom, and
(c) amino acid esters of the formula
H - B - OR<3>
wherein B is an L-amino acid residue and R<3> represents alkyl, cycloa)kyl, aryl, heteroaryl or aralkyl, in the presence of an L-specific serine carboxypeptidase enzyme, preferably carboxypeptidase Y, which has been chemically modified at the sulfhydryl group by reaction with divalent metal ions, in an aqueous solution or dispersion containing halogen or pseudohalogen ions and having a pH from about 5 to 10.5, thereby to form an insulin derivative
Ins-B-OH, Ins-B-NR<1>R<2>,
Ins-B-B-NR<1>R<2> or Ins-B-OR<3>
and subsequently cleaving a group -NR<1>R<2>, - B-NR<1>R<2>, or -OR<3>, if desired, by using a modified or unmodified serine carboxypeptidase enzyme.
<??>By using porcine insulin as substrate component and threonine as the amino acid forming part of the amine component human insulin is obtained. </p> |
