Details

Autor(en) / Beteiligte

• Østergaard, Mads
• Mishra, Narendra Kumar
• Jensen, Knud J.

Titel

The ABC of Insulin: The Organic Chemistry of a Small Protein

Ist Teil von

• Chemistry : a European journal, 2020-07, Vol.26 (38), p.8341-8357

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2020

Quelle

Wiley Online Library

Beschreibungen/Notizen

• Insulin is a small protein crucial for regulating the blood glucose level in all animals. Since 1922 it has been used for the treatment of patients with diabetes. Despite consisting of just 51 amino acids, insulin contains 17 of the proteinogenic amino acids, A‐ and B‐chains, three disulfide bridges, and it folds with 3 α‐helices and a short β‐sheet segment. Insulin associates into dimers and further into hexamers with stabilization by Zn2+ and phenolic ligands. Selective chemical modification of proteins is at the forefront of developments in chemical biology and biopharmaceuticals. Insulin's structure has made it amenable to organic and inorganic chemical reactions. This Review provides a synthetic organic chemistry perspective on this small protein. It gives an overview of key chemical and physico‐chemical aspects of the insulin molecule, with a focus on chemoselective reactions. This includes N‐acylations at the N‐termini or at LysB29 by pH control, introduction of protecting groups on insulin, binding of metal ions, ligands to control the nano‐scale assembly of insulin, and more. Insulin ABC: Insulin has been an essential drug for almost 100 years. This Review describes the chemistry of insulin, in particular, synthetic organic chemistry on insulin. This includes chemo‐ and regioselective modifications of insulin and the use of different metal ions to direct insulin self‐assembly.