Research output: Contribution to journal › Journal article › Research › peer-review
Chemical modification of peptides and proteins, such as PEGylation and lipidation, creates conjugates with new properties. However, they are typically not dynamic or stimuli-responsive. Self-assembly controlled by a stimulus will allow adjusting properties directly. Here, we report that conjugates of oligogalacturonic acids (OGAs), isolated from plant-derived pectin, are Ca2+-responsive. We report the conjugation of OGA to human insulin (HI) to create new glyco-insulins. In addition, we coupled OGA to model peptides. We studied their self-assembly by dynamic light scattering, small-angle X-ray scattering, and circular dichroism, which showed that the self-assembly to form nanostructures depended on the length of the OGA sequence and Zn2+ and Ca2+ concentrations. Subcutaneous administration of OGA12-HI with Zn2+ showed a stable decrease in blood glucose over a longer period of time compared to HI, despite the lower receptor binding affinity.
|Publication status||Published - 2023|
We thank the Villum Fonden for funding the Biomolecular Nanoscale Engineering Center (BioNEC), a Villum center of excellence, grant number VKR022710. The Novo Nordisk Foundation is acknowledged for funding the Center of Biopharmaceuticals and Biobarriers in Drug Delivery (BioDelivery), grant number NNF16OC0021948. We thank Rita Slaaby (PhD) from Novo Nordisk A/S for the receptor affinity study.
© 2023 American Chemical Society.