Insulin synthesis from natural chains by means of reversible bridging compounds - Geiger, R.; Obermeier, R. (Elsevier)
Insulin and N^α^B^"^1-trifluoroacetylinsulin were crosslinked by diaminodicarboxylic acids, preferably α,α'-diamino-suberic acid (Dsa), using bis-(tert-butyloxycarbonyl)-2.7-diaminosuberoyl-bis-(2.4.5-trichlorophenylate) [(BOC)"2-Dsa-(OTcp)"2] as coupling reagent. Elimination of the BOC groups by trifluoroacetic acid treatment and Edman degradation resulted in biologically fully active des-Phe^B"1-insulin and N^α^B^"^1-Tfa-insulin, respectively. The N^α group of the natural A-chain tetrasulfonate and the N^^B^"^2^"^9 group of the natural B-chain disulfonate, specifically trifluoroacetylated in N^α^B^"^1, were linked together by successive reaction with the above mentioned reagent. After formation of the correct disulfide bridges in high yields (60-75 %) the elimination of the connecting Dsa by Edman degradation yielded N^α^B^"^1-Tfa-insulin, which was biologically fully active.
http://dx.doi.org/10.1016/S0006-291X(73)80059-2
Keywords: W; V; U