The use of Fmoc-Lys(Pac)-OH and penicillin G acylase in the preparation of novel semisynthetic insulin analogs. |
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| Authors: | Lenka Záková Daniel Zyka Jan Jezek Ivona Hanclová Miloslav Sanda Andrzej M Brzozowski Jirí Jirácek |
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| Institution: | Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Praha 6, Czech Republic. |
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| 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 Nepsilon-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. |
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| Keywords: | insulin analogs semisynthesis phenylacetyl penicillin G acylase |
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