Mechanistic Insights into an Unusual Side-Chain-Mediated N–Cα Bond Cleavage under Collision-Induced Dissociation Conditions in the Disulfide-Containing Peptide Conopressin
| Autor: | Padmanabhan Balaram, Sunita Prakash, Sanjeev Kumar, Sahil Lall, M Achanna Venkatesha |
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| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
Collision-induced dissociation Chemistry Stereochemistry 010401 analytical chemistry Peptide Tripeptide 010402 general chemistry 01 natural sciences 0104 chemical sciences chemistry.chemical_compound Fragmentation (mass spectrometry) Structural Biology Amide Side chain Peptide bond Spectroscopy Bond cleavage |
| Zdroj: | Journal of the American Society for Mass Spectrometry. 31:1083-1092 |
| ISSN: | 1879-1123 1044-0305 |
| DOI: | 10.1021/jasms.0c00023 |
| Popis: | Conopressin, a nonapeptide disulfide CFIRNCPKG amide present in cone snail venom, undergoes a facile cleavage at the Cys6-Pro7 peptide bond to yield a disulfide bridged b6 ion. Analysis of the mass spectral fragmentation pattern reveals the presence of a major fragment ion, which is unambiguously assigned as the tripeptide sequence IRN amide. The sequence dependence of this unusual fragmentation process has been investigated by comparing it with the fragmentation patterns of related peptides, oxytocin (CYIQNCPLG amide), Lys-vasopressin (CYFQNCPKG amide), and a series of synthetic analogues. The results establish the role of the Arg4 residue in facilitating the unusual N-Cα bond cleavage at Cys6. Structures are proposed for a modified disulfide bridged fragment containing the Cys1 and Cys6 residues. Gas-phase molecular dynamics simulations provide evidence for the occurrence of conformational states that permit close approach of the Arg4 side chain to the Cys6 Cβ methylene protons. |
| Databáze: | OpenAIRE |
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