Ca2+-Responsive Glyco-insulin

Bioconjug Chem. 2023 Mar 15;34(3):518-528. doi: 10.1021/acs.bioconjchem.2c00590. Epub 2023 Feb 9.

Abstract

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 types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose
  • Calcium / metabolism
  • Circular Dichroism
  • Humans
  • Insulin* / chemistry
  • Peptides* / chemistry

Substances

  • Blood Glucose
  • Insulin
  • Peptides
  • Calcium