
@article {115053,
	title = {Mechanistic Investigations on N-C Bond Cleavages in Dibasic Peptides Containing Internal Lys and Arg Residues.},
	journal = {J Am Soc Mass Spectrom},
	year = {2022},
	month = {2022 Jul 26},
	abstract = {<p>The model nonapeptide AAARAAKAG* (* indicates amide) is used to explore N-C bond fragmentation under CID-MS conditions. Neighboring group participation and the effect of positioning of Lys and Arg residues on N-C bond cleavage is established using a library of synthetic peptide analogues. The importance of the Arg residue at position 4 and the to +3 spacing between Arg and Lys residues in determining the formation of the N-C bond cleaved product ions () is demonstrated by a comparative MS study of positional variants in analogue peptides. The effect of shortening of the Lys side chain has been established using ornithine (Orn) and diaminobutyric acid (Dab) analogues. The involvement of the Lys residue in mediating the N-C bond cleavage is further probed using N-dimethyl and isotopically labeled N lysine residues. MS experiments reveal that the ion originates from a doubly charged dehydrated ion [-18]. The mechanism of this unusual fragmentation process has been probed by using position 8 analogues (Gly, Ala, and Aib). A plausible mechanism is proposed for the origin of the ion, which involves C-terminus lactam formation followed by transannular cyclization and dehydration. The results presented in this study highlight the role of reactive side chain functionalities in promoting noncanonical fragmentation pathways.</p>
},
	issn = {1879-1123},
	doi = {10.1021/jasms.2c00055},
	author = {Kumar, Sanjeev and Venkatesha, M Achanna and Balaram, Padmanabhan}
}
@article {77446,
	title = {Mechanistic Insights into an Unusual Side-Chain-Mediated N-C Bond Cleavage under Collision-Induced Dissociation Conditions in the Disulfide-Containing Peptide Conopressin.},
	journal = {J Am Soc Mass Spectrom},
	volume = {31},
	year = {2020},
	month = {2020 May 06},
	pages = {1083-1092},
	abstract = {<p>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 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-C 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 C methylene protons.</p>
},
	issn = {1879-1123},
	doi = {10.1021/jasms.0c00023},
	author = {Kumar, Sanjeev and Venkatesha, M Achanna and Lall, Sahil and Prakash, Sunita and Balaram, Padmanabhan}
}
