Process for the selective formation of disulfide bridges in polypeptides and therapeutic compositions
Assigneeder Wissenschaften e.V. Max-Planck-Gesellschaft zur/Forderung
InventorChristian Birr
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Abstract
A process for the selective formation of at least two disulfide bridges in a polypeptide which process comprises treating a polypeptide starting material carrying at least two SH-groups to mask at least one of said SH-groups with a p-methoxybenzyl protective group and to mask at least one of the SH-groups with an acetamido methyl protective group, then splitting-off said p-methoxybenzyl protective group with pyridine-polyhydrogen fluoride in the presence of anisol, and then treating with iodine in an acid solution to produce said disulfide bridge-containing polypeptide.
Claims24
Process for the selective formation of at least two disulfide bridges in a polypeptide which process comprises treating a polypeptide starting material carrying at least four SH-groups to mask at least one of two of said SH-groups, intended to form a first disulfide bridge, with a p-methoxybenzyl protective group and to mask at least one SH-group of each further pair of SH-groups intended to form one or more further disulfide bridges, with an acetamido methyl protective group, then splitting off said p-methoxybenzyl protective group with pyridine-polyhydrogen fluoride in the presence of anisol to produce that first disulfide bridge, and then treating the polypeptide with iodine in an acid solution to produce said disulfide bridge-containing polypeptide by forming said one or more further disulfide bridges.
Process for the selective formation of at least three disulfide bridges in a polypeptide which process comprises treating a polypeptide starting material, carrying at least 6 SH-groups, to mask two of said SH-groups intended to form a first disulfide bridge with tertiary butyl mercapto protective groups, to mask at least one of two further of said SH-groups, intended to form a second disulfide bridge, with an acetamido methyl protective group, and to mask at least one SH-group of each further pair of SH-groups, intended to form one or more further disulfide bridges, with an acetamido methyl protective group, then splitting off said two tertiary butyl mercapto protective groups with tributyl phosphane under innert gas and selective oxidation with oxygen, thereby forming that first disulfide bridge, then splitting-off said p-methoxybenzyl protective group with pyridine-polyhydrogen fluoride in the presence of anisol to produce that second disulfide bridge, and then treating the polypeptide with iodine in an acid solution to produce said disulfide bridge-containing polypeptide by forming said one or more further disulfide bridges.
Dependencies are inferred from the claim text.