Insulin and solid‐phase synthesis, 1964–1970

Marglin, A.

doi:10.1002/bip.20912

Cited by 2 publications

(1 citation statement)

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“…Only upon enzymatic removal of the native 35‐residue C‐peptide is the bioactive two‐chain form of insulin produced. The single‐chain approach has been briefly exploited by chemical linkers19 and broadly adopted in the recombinant production of insulin, for which much shorter artificial C‐peptides have been developed, such as AAK or EWK 20–22. These artificial C‐peptides can be removed enzymatically to provide two‐chain insulins by the utilization of the lysine‐specific enzyme Achromobacter lyticus protease (ALP) 23…”

Section: Introductionmentioning

confidence: 99%

Total Synthesis of desB30 Insulin Analogues by Biomimetic Folding of Single‐Chain Precursors

et al. 2008

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Insulin is a peptide hormone consisting of 51 amino acids in two chains with three disulfide bridges. Human insulin and various analogues are used for the treatment of diabetes and are produced recombinantly at ton scale. Herein, we report the chemical synthesis of insulin by the step-wise, Fmoc-based, solid-phase synthesis of single-chain precursors with solubilising extensions, which under redox conditions, spontaneously fold with the correct pairing of the three disulfide bridges. The folded, single-chain, insulin precursors can be transformed into bioactive two-chain desB30 insulin by the simultaneous removal of the solubilising extension (4-5 residues) and the chain-bridging C-peptide (3-5 residues) by employing Achromobacter lyticus protease--a process well-known from the yeast-based recombinant production of insulin. The overall yields of synthetic insulins were as much as 6 %, and the synthetic process was straightforward and not labour intensive.

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