Mechanistic examination of Cβ-Cγ bond cleavages of tryptophan residues during dissociations of molecular peptide radical cations.
In this study, we used collision-induced dissociation (CID) to examine the gas-phase fragmentations of [G(n)W](•+) (n = 2-4) and [GXW](•+) (X = C, S, L, F, Y, Q) species. The C(β)-C(γ) bond cleavage of a C-terminal decarboxylated tryptophan residue ([M - CO(2)](•+)) can generate [M - CO(2) - 116](+), [M - CO(2) - 117](•+), and [1H-indole](•+) (m/z 117) species as possible product ions. Competition between the formation of [M - CO(2) - 116](+) and [1H-indole](•+) systems implies the existence of a proton-bound dimer formed between the indole ring and peptide backbone. Formation of such a proton-bound dimer is facile via a protonation of the tryptophan γ-carbon atom as suggested by density functional theory (DFT) calculations. DFT calculations also suggested the initially formed ion 2, the decarboxylated species that is active against C(β)-C(γ) bond cleavage, can efficiently isomerize to form a more stable π-radical isomer (ion 9) as supported by Rice-Ramsperger-Kassel-Marcus (RRKM) modeling. The C(β)-C(γ) bond cleavage of a tryptophan residue also can occur directly from peptide radical cations containing a basic residue. CID of [WG(n)R](•+) (n = 1-3) radical cations consistently resulted in predominant formation of [M - 116](+) product ions. It appears that the basic arginine residue tightly sequesters the proton and allows the charge-remote C(β)-C(γ) bond cleavage to prevail over the charge-directed one. DFT calculations predicted that the barrier for the former is 6.2 kcal mol(-1) lower than that of the latter. Furthermore, the pathway involving a salt-bridge intermediate also was accessible during such a bond cleavage event.
Department of Chemistry, The University of Hong Kong, Hong Kong, China.
Tao
T
Song
Ching-Yung
CY
Ma
Ivan K
IK
Chu
Chi-Kit
CK
Siu
Julia
J
Laskin
D002412:Cations / Q000737:chemistry; D005609:Free Radicals / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D011789:Quantum Theory; D013816:Thermodynamics; D014364:Tryptophan / Q000737:chemistry*
D002412:Cations; D005609:Free Radicals; D010455:Peptides; D014364:Tryptophan