Insulin-From its Discovery to the Industrial Synthesis of Modern Insulin Analogues
| Autor: | Hans-Jürgen Musiol, Luis Moroder |
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| Rok vydání: | 2017 |
| Předmět: |
Drug
Drug Industry medicine.medical_treatment media_common.quotation_subject 010402 general chemistry 01 natural sciences Chemical synthesis Catalysis chemistry.chemical_compound Diabetes mellitus Drug Discovery medicine Peptide synthesis Humans Insulin media_common Biological Products 010405 organic chemistry Chemistry General Chemistry medicine.disease Native chemical ligation Semisynthesis 0104 chemical sciences Biochemistry Chemical ligation |
| Zdroj: | Angewandte Chemie International Edition. 56:10656-10669 |
| ISSN: | 1433-7851 |
| Popis: | After the discovery of insulin as a drug for diabetes, the pharmaceutical companies were faced with the challenge to meet the demand for insulin with the highest possible degree of purity in the required quantities from animal sources. The observation of an immune reaction of patients to insulin from animal pancreatic extracts made the availability of human insulin of highest priority. Only the enzyme-catalyzed semisynthesis at the C-terminus of the insulin B-chain led to a commercial process, but it depended on porcine insulin and was aggravated by supply concerns. The advent of rDNA technology allowed the commercial preparation of human insulin by biosynthesis in virtually unlimited quantities. An increased chemical diversity was only envisaged through chemical synthesis, which was simplified by advances in solid-phase peptide synthesis and chemical ligation. Single-chain insulin precursors are now being synthesized that should enable fast screening of insulin analogues for improved biophysical, biological, and thus promising new therapeutic properties, as well as for the industrial manufacture of insulin analogues not accessible by biosynthesis. |
| Databáze: | OpenAIRE |
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