Mechanistic Insights into an Unusual Side-Chain-Mediated N-CαBond Cleavage under Collision-Induced Dissociation Conditions in the Disulfide-Containing Peptide Conopressin

Kumar, S and Venkatesha, MA and Lall, S and Prakash, S and Balaram, P (2020) Mechanistic Insights into an Unusual Side-Chain-Mediated N-CαBond Cleavage under Collision-Induced Dissociation Conditions in the Disulfide-Containing Peptide Conopressin. In: Journal of the American Society for Mass Spectrometry, 31 (5). pp. 1083-1092.

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Abstract

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. © 2021 American Society for Mass Spectrometry. Published by the American Chemical Society. All rights reserved.

Item Type:	Journal Article
Publication:	Journal of the American Society for Mass Spectrometry
Publisher:	American Chemical Society
Additional Information:	The copyright for this article belongs to American Chemical Society.
Keywords:	Amides; Dissociation; Molecular dynamics; Peptides, Collision induced dissociation; Conformational state; Disulfide-containing peptides; Fragmentation patterns; Fragmentation process; Mass spectral fragmentation; Molecular dynamics simulations; Synthetic analogues, Sulfur compounds, amide; carbene; conopressin; cysteine; disulfide; nonapeptide; oxytocin; snail venom; tripeptide; unclassified drug; vasopressin; conopressin G; disulfide, amino acid substitution; Article; carboxy terminal sequence; collisionally activated dissociation; comparative study; controlled study; disulfide bond; fragmentation reaction; gas; mass spectrometry; molecular dynamics; particle size; peptide library; peptide synthesis; protein conformation; reversed phase high performance liquid chromatography; solid phase synthesis; amino acid sequence; chemistry; molecular model; procedures; synthesis; tandem mass spectrometry, Amino Acid Sequence; Cysteine; Disulfides; Mass Spectrometry; Models, Molecular; Molecular Dynamics Simulation; Oxytocin; Protein Conformation; Tandem Mass Spectrometry
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	06 Feb 2023 09:10
Last Modified:	06 Feb 2023 09:10
URI:	https://eprints.iisc.ac.in/id/eprint/79904

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