Synthesis of insulin derivatives
US6323311A · kind A · utility
Assignee
Inventors
Key dates
| Filing date | Sep 22, 1999 |
| Grant date | Nov 27, 2001 |
| Priority date | — |
| Expiry date | Sep 22, 2019 |
Classification
- Technology area (CPC Y)Emerging Cross-Sectional Technologies
- CPC primaryY02P20/55
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
A method for the "one-pot" synthesis of insulin derivatives wherein insulin is modified at the .alpha.-amino group of the PheB1 residue is described. The method comprises protecting the .alpha.-amino group of the GlyA1 residue and the .epsilon.-amino group of the LysB29 residue by reaction of insulin with a cyclic anhydride of a dicarboxylic acid in the presence of a tertiary amine. The protected insulin is then reacted with an activated hydrophilic compound, preferably an activated polyethylene glycol, resulting in a conjugate of the hydrophilic compound coupled to the PheB1 residue of insulin. The protecting groups are then removed from the conjugate under mild acidic conditions, and the resulting insulin derivative can be purified by conventional methods. Monosubstituted insulin derivatives wherein polyethylene glycol or derivatives thereof or glycosides are coupled to the PheB1 residue of insulin are also described.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.