TY - JOUR

T1 - The ABC of Insulin

T2 - The Organic Chemistry of a Small Protein

AU - Østergaard, Mads

AU - Mishra, Narendra Kumar

AU - Jensen, Knud J.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1002/chem.202000337

DO - 10.1002/chem.202000337

M3 - Review

C2 - 32196765

VL - 26

SP - 8341

EP - 8357

JO - Chemistry: A European Journal

JF - Chemistry: A European Journal

SN - 0947-6539

IS - 38

ER -