Ca 2+ -Responsive Glyco-insulin.
Shunliang WuMads ØstergaardFreja FredholtNiels Johan ChristensenKasper K SørensenNarendra K MishraHanne Mørck NielsenKnud Jørgen JensenPublished in: Bioconjugate chemistry (2023)
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 Ca 2+ -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 Zn 2+ and Ca 2+ concentrations. Subcutaneous administration of OGA12-HI with Zn 2+ showed a stable decrease in blood glucose over a longer period of time compared to HI, despite the lower receptor binding affinity.
Keyphrases
- cancer therapy
- blood glucose
- glycemic control
- type diabetes
- drug delivery
- high resolution
- endothelial cells
- heavy metals
- protein kinase
- amino acid
- blood pressure
- magnetic resonance
- induced pluripotent stem cells
- computed tomography
- binding protein
- magnetic resonance imaging
- mass spectrometry
- pluripotent stem cells
- metabolic syndrome
- monte carlo
- capillary electrophoresis
- adipose tissue
- dual energy