Østergaard Mads, Mishra Narendra Kumar, Jensen Knud J
Department of Chemistry, University of Copenhagen, Thorvaldsensvej 40, 1871, Frederiksberg C, Denmark.
Chemistry. 2020 Jul 8;26(38):8341-8357. doi: 10.1002/chem.202000337. Epub 2020 May 14.
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 Zn 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 Lys by pH control, introduction of protecting groups on insulin, binding of metal ions, ligands to control the nano-scale assembly of insulin, and more.
胰岛素是一种对调节所有动物血糖水平至关重要的小蛋白质。自1922年以来，它一直被用于治疗糖尿病患者。尽管胰岛素仅由51个氨基酸组成，但它包含17种蛋白质ogenic氨基酸、A链和B链、三个二硫键，并且以3个α螺旋和一个短β折叠片段折叠。胰岛素通过锌和酚类配体稳定形成二聚体，并进一步形成六聚体。蛋白质的选择性化学修饰处于化学生物学和生物制药发展的前沿。胰岛素的结构使其适合有机和无机化学反应。本综述从合成有机化学的角度对这种小蛋白质进行了阐述。它概述了胰岛素分子的关键化学和物理化学方面，重点是化学选择性反应。这包括通过pH控制在N端或赖氨酸处进行N-酰化、在胰岛素上引入保护基团、金属离子的结合、控制胰岛素纳米级组装的配体等等。
