Totalsynthese von Humaninsulin unter gezielter Bildung der Disulfidbindungen. Vorläufige Mitteilung

✍ Scribed by Peter Sieber; Bruno Kamber; Albert Hartmann; Albert Jöhl; Bernhard Riniker; Werner Rittel

• Publisher: John Wiley and Sons
• Year: 1974
• Tongue: German
• Weight: 327 KB
• Volume: 57
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19740570839

✦ Synopsis

A preliminary account is given of a total synthesis of human insulin involving directed formation of the three disulfide bonds at different stages of the fragment‐condensation approach. The synthesis was facilitated by the application of two new methods for the selective removal of protecting groups. In the first, two S‐Trt‐protected cysteine residues are converted to the disulfide without affecting S‐Acm‐protected cysteine residues. The second new method consists in a very mild, pH‐controlled, acidolysis of N(α)‐Trt, leaving intact N(α)‐Bpoc and other acid‐labile protecting groups. The last step of the synthesis was the formation of the disulfide bridge between the Acm‐protected cysteine residues A7 and B7 by iodine. Extensive counter‐current distribution yielded the synthetic hormone in pure form. It was compared and found to be identical with natural human insulin. Identification was achieved by means of thinlayer chromatography and electrophoretic procedures, as well as by comparing the pattern of break‐down by enzymes (finger‐printing). The natural and synthetic hormones were crystallized under identical conditions. The synthetic human insulin was found to possess full biological activity in an in vitro system.