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Updated: Jul 30, 2026
08:09
Peptide Scanning-assisted Identification of a Monoclonal Antibody-recognized Linear B-cell Epitope
Published on: March 24, 2017
Carbacyclic peptide mimetics as VCAM-VLA-4 antagonists.
J Tilley1, G Kaplan, N Fotouhi
1Roche Research Center, Hoffmann-La Roche Inc, Nutley, NJ 07110, USA. jefferson.tilley@roche.com
Bioorganic & Medicinal Chemistry Letters
|June 24, 2000
Summary
Researchers created peptide analogues by replacing sulfur with carbon using a Wittig reaction. These
Area of Science:
- Medicinal Chemistry
- Organic Synthesis
- Peptide Chemistry
Background:
- Cyclic disulfides are crucial structural motifs in bioactive peptides.
- The VCAM-VLA-4 interaction is a key target in inflammatory diseases.
Purpose of the Study:
- To synthesize novel cyclic peptide analogues by replacing disulfide bonds with carbon atoms.
- To evaluate the biological activity of these 'carba' analogues in a VCAM-VLA-4 binding assay.
Main Methods:
- Intramolecular Wittig reaction for carbon-sulfur bond substitution.
- Synthesis of 13-membered cyclic peptide scaffolds.
- Assessment of VCAM-VLA-4 binding affinity.
Main Results:
- Successfully generated 'carba' analogues of a cyclic disulfide peptide.
- Potency in the VCAM-VLA-4 assay was found to be sensitive to ring size.
- The synthesized analogues exhibited lower potency compared to the parent disulfide.
Conclusions:
- Carbon-sulfur substitution is feasible for creating cyclic peptide analogues.
- The VCAM-VLA-4 binding activity is influenced by the replacement of sulfur with carbon and ring size.
- Further optimization may be needed to restore or enhance potency.
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