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Probing the correlation between insulin activity and structural stability through introduction of the rigid A6-A11 bond

Ong, Shee Chee; Belgi, Alessia; van Lierop, Bianca; Delaine, Carlie; Andrikopoulos, Sofianos; MacRaild, Christopher A.; Norton, Raymond S.; Haworth, Naomi; Robinson, Andrea; Forbes, Briony


The development of fast-acting and highly stable insulin analogues is challenging. Insulin undergoes structural transitions essential for binding and activation of the insulin receptor (IR), but these conformational changes can also affect insulin stability. Previously, we substituted the insulin A6–A11 cystine with a rigid, non-reducible C=C linkage (“dicarba” linkage). A cis-alkene permitted the conformational flexibility of the A-chain N-terminal helix necessary for high-affinity IR binding,...[Show more]

CollectionsANU Research Publications
Date published: 2018
Type: Journal article
Source: Journal of Biological Chemistry
DOI: 10.1074/jbc.RA118.002486
Access Rights: Open Access


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