The use of Fmoc-Lys(Pac)-OH and penicillin G acylase in the preparation of novel semisynthetic insulin analogs.
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.
Záková
Lenka
L
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Praha 6, Czech Republic.
Zyka
Daniel
D
Jezek
Jan
J
Hanclová
Ivona
I
Sanda
Miloslav
M
Brzozowski
Andrzej M
AM
Jirácek
Jirí
J
D000818:Animals; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010399:Penicillin Amidase / Q000737:chemistry*; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism
D007328:Insulin; D009842:Oligopeptides; D011972:Receptor, Insulin; D010399:Penicillin Amidase