Weitzel G, Bauer F U, Eisele K
Hoppe Seylers Z Physiol Chem. 1978 Aug;359(8):945-58. doi: 10.1515/bchm2.1978.359.2.945.
The desonapeptide-(B22--30)-insulin pentamethyl ester, protected with Boc- at the two N-terminal amino groups, was prepared as described in the preceding XVth communication[6]. The free carboxyl group of the glutamic acid residue B21 of this compound was coupled to the following synthetic oligopeptide esters (X = Lys or Ala): X-Gly-OMe X-Gly-Phe-OMe X-Gly-Phe-Phe-OME X-Gly-Phe-Phe-Tyr-OMe X-Gly-Phe-Phe-Tyr-Ala-OMe After coupling, the semisynthetic products were deprotected and purified. Their biological activities were determined in the mouse fall test and by measurement of blood glucose levels. There were no statistical differences between the values obtained for the lysine B22 and alanine B22 products. The three-step increase in activity due to the amino acids Phe-Phe-Tyr (B24--26) was still recognizable, but compared with the analogues containing arginine B22, the activities were very stronly diminished. These results are in contrast with the assumption that activity of insulin is dependent on the formation of a strong ionic linkage between the asparagine-A21 carboxyl group and any positive charge in B22. The results, however, demonstrate the high specificity of the arginine guanidino group in position B22.
去氨肽 -（B22 - 30）- 胰岛素五甲酯，其两个N末端氨基用Boc保护，按照前文第十五篇通讯[6]所述方法制备。该化合物谷氨酸残基B21的游离羧基与下列合成寡肽酯偶联（X = Lys或Ala）：X - Gly - OMe、X - Gly - Phe - OMe、X - Gly - Phe - Phe - OMe、X - Gly - Phe - Phe - Tyr - OMe、X - Gly - Phe - Phe - Tyr - Ala - OMe。偶联后，对半合成产物进行脱保护和纯化。通过小鼠跌落试验和测量血糖水平来测定它们的生物活性。赖氨酸B22和丙氨酸B22产物所得值之间无统计学差异。由氨基酸Phe - Phe - Tyr（B24 - 26）引起的活性三步增加仍可识别，但与含精氨酸B22的类似物相比，活性显著降低。这些结果与胰岛素活性取决于天冬酰胺 - A21羧基与B22中任何正电荷之间形成强离子键的假设相反。然而，结果表明B22位精氨酸胍基具有高度特异性。
