Ca2+-Responsive Glyco-insulin
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Ca2+-Responsive Glyco-insulin. / Wu, Shunliang; Østergaard, Mads; Fredholt, Freja; Christensen, Niels Johan; Sørensen, Kasper K.; Mishra, Narendra K.; Nielsen, Hanne M.; Jensen, Knud J.
I: Bioconjugate Chemistry, Bind 34, Nr. 3, 2023, s. 518–528.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Ca2+-Responsive Glyco-insulin
AU - Wu, Shunliang
AU - Østergaard, Mads
AU - Fredholt, Freja
AU - Christensen, Niels Johan
AU - Sørensen, Kasper K.
AU - Mishra, Narendra K.
AU - Nielsen, Hanne M.
AU - Jensen, Knud J.
N1 - Funding Information: 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. Publisher Copyright: © 2023 American Chemical Society.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1021/acs.bioconjchem.2c00590
DO - 10.1021/acs.bioconjchem.2c00590
M3 - Journal article
C2 - 36756787
AN - SCOPUS:85147891598
VL - 34
SP - 518
EP - 528
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
SN - 1043-1802
IS - 3
ER -
ID: 337977003