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The use of Fmoc-Lys(Pac)-OH and penicillin G acylase in the preparation of novel semisynthetic insulin analogs

✍ Scribed by Lenka Žáková; Daniel Zyka; Jan Ježek; Ivona Hančlová; Miloslav Šanda; Andrzej M. Brzozowski; Jiří Jiráček


Publisher
John Wiley and Sons
Year
2007
Tongue
English
Weight
241 KB
Volume
13
Category
Article
ISSN
1075-2617

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✦ Synopsis


Abstract

In this paper, we present the detailed synthetic protocol and characterization of Fmoc‐Lys(Pac)‐OH, its use for the preparation of octapeptides H‐Gly‐Phe‐Tyr‐N‐MePhe‐Thr‐Lys(Pac)‐Pro‐Thr‐OH and H‐Gly‐Phe‐Phe‐His‐Thr‐Pro‐Lys(Pac)‐Thr‐OH by solid‐phase synthesis, trypsin‐catalyzed condensation of these octapeptides with desoctapeptide(B23‐B30)‐insulin, and penicillin G acylase catalyzed cleavage of phenylacetyl (Pac) group from N^ε^‐amino group of lysine to give novel insulin analogs [TyrB25, N‐MePheB26,LysB28,ProB29]‐insulin and [HisB26]‐insulin. These new analogs display 4 and 78% binding affinity respectively to insulin receptor in rat adipose membranes. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.