Journal
BIOMACROMOLECULES
Volume 18, Issue 3, Pages 965-975Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.6b01830
Keywords
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Funding
- Canada Research Chair on Protein-enhanced Biomaterials
- Canada Research Chair in Applied Metabolic Engineering
- Natural Sciences and Engineering Research Council of Canada
- Fonds de recherche du Quebec Nature et technologies
- MEDITIS training program
- Biomedical Science and Technology Research Group
- John Stewart Endowed Chair in Peptide Chemistry
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We have developed a heterodimeric coiled-coil system based on two complementary peptides, namely (EVSALEK)(5) and (ICVSALKE)(s), or E and K, for the attachment of E-tagged biomolecules onto K-decorated biomaterials. We here explore two approaches to control the strength and the stability of the E/K coiled-coil complex, and thus its potential for the controlled release of biomolecules. Those are Leucine-to-Alanine mutations in the K peptide (4 peptides with 0 to 3 mutations) and multivalent presentation of the E peptide (6 bio-objects from monomeric to dimeric and n-meric). Using E-tagged growth factors and nanoparticles as models, SPR-based assays performed under continuous flow indicated that the release rate was strongly affected by both approaches independently, and that the strength of the capture could be finely tuned over a wide range (apparent dissociation constant from 0.12 pM to 270 nM). Further release assays carried out in well-plates showed that the multivalent presentation only had a significant influence in this setup since the wells were not rinsed under continuous flow.
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