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Backbone cyclic insulin
Author(s) -
Andersen Asser S.,
Palmqvist Eva,
Bang Susanne,
Shaw Allan C.,
Hubalek Frantisek,
Ribel Ulla,
HoegJensen Thomas
Publication year - 2010
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.1264
Subject(s) - insulin , proteolysis , chemistry , peptide , cyclic peptide , stereochemistry , insulin receptor , biochemistry , enzyme , biology , endocrinology , insulin resistance
Abstract Backbone cyclic insulin was designed and prepared by reverse proteolysis in partial organic solvent of a single‐chain precursor expressed in yeast. The precursor contains two loops to bridge the two chains of native insulin. The cyclisation method uses Achromobacter lyticus protease and should be generally applicable to proteins with C ‐terminal lysine and proximal N ‐terminal. The presence of the ring‐closing bond and the native insulin disulfide patterns were documented by LC–MS peptide maps. The cyclic insulin was shown to be inert towards degradation by CPY, but was somewhat labile towards chymotrypsin. Intravenous administration of the cyclic insulin to Wistar rats showed the compounds to be equipotent to HI despite much lower insulin receptor affinity. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.