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Culturing Mammalian Cells in Three-dimensional Peptide Scaffolds
Published on: June 13, 2018
A sucrose-derived scaffold for multimerization of bioactive peptides
Venkataramanarao Rao1, Ramesh Alleti, Liping Xu
1Department of Chemistry and Biochemistry, The University of Arizona, Tucson, AZ 85721-0041, USA.
Bioorganic & Medicinal Chemistry
|September 24, 2011
Summary
Multivalent molecular scaffolds were created using sucrose and peptide azides. Multivalent CCK4 constructs showed enhanced binding potency, suggesting multivalent interactions, unlike MSH4 constructs.
Area of Science:
- Medicinal Chemistry
- Supramolecular Chemistry
- Chemical Biology
Background:
- Peptide-based ligands are crucial for targeting specific receptors.
- Multivalent interactions can enhance ligand binding affinity and efficacy.
- Developing novel scaffolds for presenting multiple ligands is essential for drug discovery.
Purpose of the Study:
- To synthesize a spherical molecular scaffold and conjugate it with peptide ligands.
- To investigate the binding characteristics of monovalent and multivalent constructs using competitive binding assays.
- To explore the impact of scaffold presentation on ligand-receptor interactions.
Main Methods:
- Spherical molecular scaffold synthesis from sucrose.
- Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) for ligand conjugation.
- Competitive binding assays using Eu-labeled probes and engineered Hek293 cells overexpressing MC4R and CCK2R.
Main Results:
- Monovalent and multivalent MSH4 constructs showed binding comparable to the parental ligand.
- Monovalent CCK4 constructs were less potent than the parental ligand.
- Multivalent CCK4 constructs exhibited equal or greater potency than the parental ligand, indicating multivalent binding.
Conclusions:
- The scaffold effectively presented peptide ligands for receptor binding studies.
- Multivalent CCK4 constructs demonstrate enhanced binding, likely due to increased residence time and multivalent interactions.
- MSH4 constructs did not show enhanced binding, suggesting limitations in ligand spacing or intrinsic binding affinity for multivalent engagement.
