A1 Refereed original research article in a scientific journal
Influence of the Assembly State on the Functionality of a Supramolecular Jagged1-Mimicking Peptide Additive
Authors: Matilde Putti, Oscar M. J. A. Stassen, Maaike J. G. Schotman, Cecilia M. Sahlgren, Patricia Y. W. Dankers
Publisher: AMER CHEMICAL SOC
Publication year: 2019
Journal: ACS Omega
Journal name in source: ACS OMEGA
Journal acronym: ACS OMEGA
Volume: 4
Issue: 5
First page : 8178
Last page: 8187
Number of pages: 10
ISSN: 2470-1343
eISSN: 2470-1343
DOI: https://doi.org/10.1021/acsomega.9b00869
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/41129211
Expanding the bioactivation toolbox of supramolecular materials is of utmost relevance for their broad applicability in regenerative medicines. This study explores the functionality of a peptide mimic of the Notch ligand Jagged1 in a supramolecular system that is based on hydrogen bonding ureido-pyrimidinone (UPy) units. The functionality of the peptide is studied when formulated as an additive in a supramolecular solid material and as a self-assembled system in solution. UPy conjugation of the DSLJAG1 peptide sequence allows for the supramolecular functionalization of UPy-modified polycaprolactone, an elastomeric material, with UPy-DSLJAG1. Surface presentation of the UPy-DSLJAG1 peptide was confirmed by atomic force microscopy and X-ray photoelectron spectroscopy analyses, but no enhancement of Notch activity was detected in cells presenting Notch1 and Notch3 receptors. Nevertheless, a significant increase in Notch-signaling activity was observed when DSLJAG1 peptides were administered in the soluble form, indicating that the activity of DSLJAG1 is preserved after UPy functionalization but not after immobilization on a supramolecular solid material. Interestingly, an enhanced activity in solution of the UPy conjugate was detected compared with the unconjugated DSLJAG1 peptide, suggesting that the self-assembly of supramolecular aggregates in solution ameliorates the functionality of the molecules in a biological context.
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