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Updated: Jun 28, 2026
07:11
Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
A cyclodecapeptide ligand to vitamin B12
Vincent Duléry1, Nicolas A Uhlich, Noélie Maillard
1Département de Chimie Moléculaire-UMR-CNRS 5250 & ICMG FR 2607, Université Joseph Fourier, BP 51, 38041, Grenoble Cedex 9, France.
Organic & Biomolecular Chemistry
|October 31, 2008
Summary
Researchers developed novel cyclic peptides that bind vitamin B12 derivatives with high affinity. These histidine and cysteine-containing peptides offer enhanced stability for the vitamin B12 metal center.
Area of Science:
- Biochemistry
- Medicinal Chemistry
- Structural Biology
Background:
- Vitamin B12 (cobalamin) is essential for various biological processes.
- Developing synthetic ligands for vitamin B12 is crucial for understanding its coordination chemistry and for potential therapeutic applications.
- Cyclic peptides offer a stable scaffold for designing specific molecular interactions.
Purpose of the Study:
- To synthesize and characterize novel cyclic peptide ligands for vitamin B12 derivatives.
- To investigate the binding affinities and coordination modes of these peptides to aquocobalamin.
- To explore the structural basis for enhanced stability of the cyclopeptide-cobalamin complex.
Main Methods:
- Screening of cyclic decapeptide libraries against vitamin B12 derivatives.
- Chemical synthesis and purification of identified cyclic peptide ligands.
- Binding affinity studies using techniques like spectroscopy.
- Solution structure determination using proton nuclear magnetic resonance ((1)H NMR).
Main Results:
- Identified and synthesized two cyclic peptides, cyclo-(HisAspGluProGlyIleAlaThrProdGln) and cyclo-(ValAspGluProGlyGluAspCysProdGln).
- These peptides bind aquocobalamin with high affinities (K(a) ≈ 10(5) M(-1)) through coordination of histidine or cysteine residues to the cobalt center.
- Solution structure analysis revealed interactions between peptide side chains and the vitamin B12 corrin ring.
- The histidine-containing cyclopeptide-cobalamin complex demonstrated increased stability against cyanide exchange.
Conclusions:
- Novel cyclic peptides incorporating histidine and cysteine effectively coordinate with vitamin B12.
- The designed peptides exhibit high binding affinities and can stabilize the vitamin B12 metal center.
- These findings provide insights into the design of peptide-based chelators for metalloenzymes and potential therapeutic agents.
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