Enzyme-assisted semisynthesis of shortened B26-modified insulins

Abstract

The role of the invariant residue B26-tyrosine in determining the structural and biological properties of insulin has been extensively investigated by the use of semisynthetic des-(B27-B30)-insulins with modifications of position B26. Apart from the conventional trypsin-catalyzed peptide bond formation between the C-terminal amino acid ArgB22 of des-(B23-B30)-insulin and synthetic tetrapeptides we elaborated a new approach using des-(B26-B30)-insulin as substrate in alpha-chymotrypsin-mediated syntheses. Results obtained from bioassays and CD-spectroscopy underline the importance of position B26 to the association of the native molecule and to the modulation of structural and hormonal properties of shortened insulins.