Assigning Structures to Gas-Phase Peptide Cations and Cation-Radicals. An Infrared Multiphoton Dissociation, Ion Mobility, Electron Transfer, and Computational Study of a Histidine Peptide Ion

Andrikopoulos

Řezáč

et al. 2016

Abstract. Noncovalent complexes of hydrophobic peptides GLLLG and GLLLK with photoleucine (L*) tagged peptides G(L* n L m )K (n = 1,3, m = 2,0) were generated as singly charged ions in the gas phase and probed by photodissociation at 355 nm. Carbene intermediates produced by photodissociative loss of N 2 from the L* diazirine rings underwent insertion into X−H bonds of the target peptide moiety, forming covalent adducts with yields reaching 30%. Gas-phase sequencing of the covalent adducts revealed preferred bond formation at the C-terminal residue of the target peptide. Site-selective carbene insertion was achieved by placing the L* residue in different positions along the photopeptide chain, and the residues in the target peptide undergoing carbene insertion were identified by gas-phase ion sequencing that was aided by specific 13 C labeling. Density functional theory calculations indicated that noncovalent binding to GL*L*L*K resulted in substantial changes of the (GLLLK + H) + ground state conformation. The peptide moieties in [GL*L*LK + GLLLK + H] + ion complexes were held together by hydrogen bonds, whereas dispersion interactions of the nonpolar groups were only secondary in ground-state 0 K structures. Born-Oppenheimer molecular dynamics for 100 ps trajectories of several different conformers at the 310 K laboratory temperature showed that noncovalent complexes developed multiple, residue-specific contacts between the diazirine carbons and GLLLK residues. The calculations pointed to the substantial fluidity of the nonpolar side chains in the complexes. Diazirine photochemistry in combination with Born-Oppenheimer molecular dynamics is a promising tool for investigations of peptide-peptide ion interactions in the gas phase.

Section: Computationsmentioning

confidence: 99%

Efficient Covalent Bond Formation in Gas-Phase Peptide–Peptide Ion Complexes with the Photoleucine Stapler

Andrikopoulos

Řezáč

et al. 2016

“…Conformational search of GL*GG-amide ions was performed according to a previously reported procedure [13]. First, GLGG-amide ions were generated by the ConformSearch engine [13] that rapidly converged to yield 20 low-energy ion conformers.…”

Section: Calculationsmentioning

confidence: 99%

“…First, GLGG-amide ions were generated by the ConformSearch engine [13] that rapidly converged to yield 20 low-energy ion conformers. In these, a methyl group in each leucine residue was rebuilt into an L* diazirine ring, and the conformers were fully optimized using DFT gradient optimization.…”

Section: Calculationsmentioning

confidence: 99%

Photoleucine Survives Backbone Cleavage by Electron Transfer Dissociation. A Near-UV Photodissociation and Infrared Multiphoton Dissociation Action Spectroscopy Study

Martens

Marek

et al. 2016

Abstract. We report a combined experimental and computational study aimed at elucidating the structure of N-terminal fragment ions of the c type produced by electron transfer dissociation of photo-leucine (L*) peptide ions GL*GGKX. The c 4 ion from GL*GGK is found to retain an intact diazirine ring that undergoes selective photodissociation at 355 nm, followed by backbone cleavage. Infrared multiphoton dissociation action spectra point to the absence in the c 4 ion of a diazoalkane group that could be produced by thermal isomerization of vibrationally hot ions. The c 4 ion from ETD of GL*GGK is assigned an amide structure by a close match of the IRMPD action spectrum and calculated IR absorption. The energetics and kinetics of c 4 ion dissociations are discussed.

“…First, a full conformational search was carried out using the ConformSearch engine [21,22] for analogous (GLGGR +2H) 2+ ions containing standard amino acid residues for which there are molecular dynamics parameters. The procedure consists of molecular dynamics mapping of the conformational space in a replica-exchange format [23] using the NAMD program [24] and the CHARMM force field [25].…”

Section: Computationsmentioning

confidence: 99%

Electron Transfer Reduction of the Diazirine Ring in Gas-Phase Peptide Ions. On the Peculiar Loss of [NH₄O] from Photoleucine

Marek

Pepin

et al. 2014

Self Cite

Abstract. Electron transfer to gas-phase peptide ions with diazirine-containing amino acid residue photoleucine (L*) triggers diazirine ring reduction followed by cascades of residue-specific radical reactions. Upon electron transfer, substantial fractions of (GL*GGR +2H) +• cation-radicals undergo elimination of [NH O-labeled peptide ions and found to specifically involve the amide oxygen of the N-terminal residue. The structures, energies, and electronic states of the peptide radical species were elucidated by a combination of near-UV photodissociation experiments and electron structure calculations combining ab initio and density functional theory methods. Electron transfer reaching the ground electronic states of charge reduced (GL*GGR +2H) +• cation-radicals was found to reduce the diazirine ring. In contrast, backbone N−C α bond dissociations that represent a 60%-75% majority of all dissociations because of electron transfer are predicted to occur from excited electronic states.