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Preparing a 68Ga-labeled Arginine Glycine Aspartate (RGD)-peptide for Angiogenesis
Published on: January 7, 2019
Multivalent RGD synthetic peptides as potent alphaVbeta3 integrin ligands
Elisabeth Garanger1, Didier Boturyn, Jean-Luc Coll
1Ingénierie Moléculaire et Chimie Bioorganique, LEDSS, CNRS UMR 5616, ICMG FR 2607, Université Joseph Fourier, BP 53, 38041 Grenoble Cedex 9, France.
Organic & Biomolecular Chemistry
|May 12, 2006
Summary
Multivalency enhances alphaVbeta3-ligand activity. Ligands with three and four clustered cyclo[-RGDfK-] peptides effectively inhibited alphaVbeta3-specific antibody binding in vitro.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Discovery
Background:
- Integrin alphaVbeta3 is a key target in cancer therapy.
- Multivalency can enhance ligand-receptor interactions.
- Cyclic peptides like RGD are potent alphaVbeta3 ligands.
Purpose of the Study:
- To investigate the multivalency effect of clustered alphaVbeta3 ligands.
- To synthesize and evaluate cyclodecapeptide-based ligands with varying numbers of RGD motifs.
- To determine the optimal ligand density for alphaVbeta3 inhibition.
Main Methods:
- Synthesis of RAFT(c[-RGDfK-])n derivatives with 1 to 16 RGD motifs.
- In vitro assays using alphaVbeta3-expressing cells.
- Measurement of 23C6 monoclonal antibody fixation inhibition.
Main Results:
- Ligands with three and four clustered cyclo[-RGDfK-] peptides showed significant inhibition.
- The multivalency effect was clearly demonstrated, with optimal activity at low-to-moderate ligand densities.
- A dose-dependent inhibition of antibody binding was observed.
Conclusions:
- Multivalency significantly enhances the inhibitory activity of alphaVbeta3 ligands.
- Cyclodopeptide scaffolds can effectively present multiple RGD motifs for potent alphaVbeta3 targeting.
- These findings support the development of multivalent RGD-based therapeutics.
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