Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/17969
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Type: Journal article
Title: The unusual loss of an internal Val residue from the (M-H)- parent anions of the antimicrobial peptide citropin 1.1 and synthetically modified analogues - Fragmentations which require a specific conformation of the decomposing anion
Author: Brinkworth, C.
Bilusich, D.
Bowie, J.
Citation: International Journal of Mass Spectrometry, 2004; 236(1-3):43-53
Publisher: Elsevier Science BV
Issue Date: 2004
ISSN: 1387-3806
1873-2798
Statement of
Responsibility: 
Craig S. Brinkworth, Daniel Bilusich and John H. Bowie
Abstract: The electrospray negative ion mass spectra of citropin 1.1 (GLFDVIKKVASVIGGL-NH2) and of synthetically modified analogues show loss of an internal Val residue from both the (M - H)- anion and certain fragment anions. The negative ion spectra of GLFDVIQQVASVIGGL-NH 2 and of three synthetically modified versions where Val residues are successively replaced by Ile shows that it is Val12 which is eliminated. A joint experimental and theoretical study indicates that this internal rearrangement requires the decomposing anion to have an α-helical structure in the reaction region. If the conformation of the anion is randomised, either by increasing the internal energy of the decomposing (M - H)- anion, or by making the electrospray solution strongly acidic or strongly basic, the [(M - H) - Val]- fragmentation is either reduced or no longer observed. Using isopropanol (rather than water/acetonitrile) as the electrospay solvent enhances the abundances of [(M - H) - Val]- peaks (compared with normal backbone cleavage peaks) up to 30 times. The process is initiated by the C-terminal CONH- group reacting at the carbonyl centre of the amide function situated between Ser11 and Val12. The reacting groups can approach to within 2.5 Å when the peptide has an α-helical structure in the reaction region. Nucleophilic substitution followed by decomposition of the tetrahedral intermediate gives a rearranged peptide with the original Val12 now occupying the C-terminal position. Calculations at the HF/6-31G(d)//HF/6-31G(d) level of theory indicate that formation of the initial tetrahedral intermediate is exothermic (-11.9 kcal mol-1) with the rearrangement sequence being endothermic (17.1 kcal mol-1). The overall reaction requires the (M - H)- anion to have an excess energy of 40.8 kcal mol-1 at the level of theory used in this study. The [Aspγ-H2O-CH2O]- fragment anion in the negative ion spectrum of citropin 1.1 rearranges to a similar tetrahedral intermediate which undergoes competitive loss of Val and cleavage of the peptide backbone. These reactions require the [Aspγ-H 2O-CH2O]- decomposing anion to have a helical structure in the vicinity of the reaction centre. © 2004 Elsevier B.V. All rights reserved.
Description: Copyright © 2004 Elsevier B.V. All rights reserved.
DOI: 10.1016/j.ijms.2004.05.011
Description (link): http://www.elsevier.com/wps/find/journaldescription.cws_home/500847/description#description
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