A SHORTENED INSULIN WITH FULL INVITRO POTENCY
A SHORTENED INSULIN WITH FULL INVITRO POTENCY
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DOI：
10.1515/bchm3.1985.366.1.521
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发表时间：
1985-01-01
期刊：
影响因子：
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通讯作者：
ZAHN, H
中科院分区：
文献类型：
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作者：
FISCHER, WH;SAUNDERS, D;ZAHN, H
以受保护的Des[(B23-30)-八肽]胰岛素（猪）和H-Gly-Phe-Phe-NH2为原料，经胰蛋白酶介导半合成制备Des[(B026-30)-五肽]胰岛素- b25 -酰胺，产率为9%（以胰岛素为基础）。用化学、生物功能和圆二色光谱对该类似物进行了表征。des[(B26-30)-五肽]胰岛素与游离羧酸组在体外表现出典型的胰岛素活性仅为25%，而des[(B26-30)-五肽]胰岛素酰胺具有充分的活性。因此，des[(B26-30)-五肽]胰岛素在phb25疏水环境中的负电荷被中和的前提下，满足了受体识别和结合以及发挥生物效应的所有结构和动力学要求。
Des[(B026-30)-pentapeptide]insulin-B25-amide was prepared from protected des[(B23-30)-octapeptide]insulin (pig) and H-Gly-Phe-Phe-NH2 by trypsin-mediated semisynthesis in a yield of 9% (based on insulin). The analog was characterized with respect to chemistry, biological function and CD [circular dichroism] spectroscopy. While des[(B26-30)-pentapeptide]insulin with free carboxylate group exhibited a typical insulin activity of only 25% in vitro, des[(B26-30)-pentapeptide]insulinamide was fully active. Therefore des[(B26-30)-pentapeptide] insulin meets all structural and dynamic requirements for recognition and binding of the receptor as well as exertion of the biological effect, provided that the negative charge in the hydrophobic environment of PheB25 is neutralized.