Insulin-From its Discovery to the Industrial Synthesis of Modern Insulin Analogues.

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ID: 64244
2017
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Ranked #46 of 192 articles by views in angewandte chemie (international ed in english)

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Abstract
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.
Reference Key
moroder2017insulinfromangewandte Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Moroder, Luis;Musiol, Hans-Jürgen;
Journal angewandte chemie (international ed in english)
Year 2017
DOI
10.1002/anie.201702493
URL
Keywords
insulin biosynthesis native chemical ligation semisynthesis solid-phase synthesis

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