Fragmentation of Singly Charged Peptide Ions by Photodissociation at <i>λ</i>=157 nm

Thompson, Matthew S.; Cui, Weidong; Reilly, James P.

doi:10.1002/anie.200460788

Cited by 148 publications

(188 citation statements)

References 23 publications

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“…Photodissociation (PD) is an alternative method for generating radicals by electronic excitation of a suitable precursor [18]. Undesirable side reactions are avoided with PD due to the specificity of the excitation chemistry.…”

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confidence: 99%

Tracking radical migration in large hydrogen deficient peptides with covalent labels: Facile movement does not equal indiscriminate fragmentation

Julian

2009

J. Am. Soc. Mass Spectrom.

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Photodissociation of iodo-tyrosine modified peptides yields localized radicals on the tyrosine side chain, which can be further dissociated by collisional activation. We have performed extensive experiments on model peptides, RGYALG, RGYG, and their derivatives, to elucidate the mechanisms underlying backbone fragmentation at tyrosine. Neither acetylation nor deuteration of the tyrosyl phenolic hydrogen significantly affects backbone fragmentation. However, deuterium migration from the tyrosyl ␤ carbon is concomitant with cleavage at tyrosine. Substitution of tyrosine with 4-hydroxyphenylglycine, which does not have ␤ hydrogens, results in almost complete elimination of backbone fragmentation at tyrosine. These results suggest that a radical situated on the ␤ carbon is required for a-type fragmentation in hydrogen-deficient radical peptides. Replacement of the ␣H of the residue adjacent to tyrosine with methyl groups results in significant diminution of backbone fragmentation. The initial radical abstracts an ␣H from the adjacent amino acid, which is poised to "rebound" and abstract the ␤H of tyrosine through a six-membered transition-state. Subsequent ␤-scission leads to the observed a-type backbone fragment. These results from deuterated peptides clearly reveal that radical migration in peptides can occur and that multiple migrations are not infrequent. Counterintuitively, close examination of all experimental results reveals that the probability for fragmentation at a particular residue is well correlated with thermodynamic radical stability. A-type fragmentation therefore appears to be most likely when favorable thermodynamics are combined with the relevant kinetic control. These results are consistent with ab initio calculations, which demonstrate that barriers to migration are significantly smaller in magnitude than probable dissociation thresholds. (J Am Soc

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Tracking radical migration in large hydrogen deficient peptides with covalent labels: Facile movement does not equal indiscriminate fragmentation

Julian

2009

J. Am. Soc. Mass Spectrom.

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“…Melittin, kassinin, Lys [0]bradykinin, bradykinin, dynorphin-␤, GSK-␤ ␤ inhibitor, myosin kinase inhibitor, and mouse ANP [1][2][3][4][5][6][7][8][9][10][11] were purchased from American Peptide Company (Sunnyvale, CA). Polyalanine peptides were synthesized in-house using standard Fmoc coupling methodology.…”

Section: Methodsmentioning

confidence: 99%

“…It is demonstrated that a naphthyl based 18-crown-6 adduct is ideally suited for attaching to a variety peptides and fragmenting them following absorption of 266 nm light. [7][8][9][10][11]. Though none of these techniques is perfect, each has characteristic strengths and weaknesses.…”

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confidence: 99%

“…here are a variety of mainstream fragmentation methodologies available for interrogating peptides, including collision-induced dissociation (CID) [1], infrared multiphoton photodissociation (IRMPD) [2], electron capture dissociation (ECD) [3], and electron-transfer dissociation (ETD) [4]. In addition, there are other methods that can be used, such as surface induced dissociation (SID) [5], black-body infrared radiative dissociation (BIRD) [6], along with various photodissociation experiments employing high-energy lasers [7][8][9][10][11]. Though none of these techniques is perfect, each has characteristic strengths and weaknesses.…”

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Rapid peptide fragmentation without electrons, collisions, infrared radiation, or native chromophores

Yeh

Sun

Meneses

et al. 2009

J. Am. Soc. Mass Spectrom.

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Ultraviolet photodissociation of peptides followed by mass analysis has several desirable advantages relative to other methods, yet it has not found widespread use due to several limitations. One shortcoming is the inefficiency with which peptides absorb in the ultraviolet. This issue has a simple solution and can be circumvented by the attachment of noncovalent adducts that contain appropriate chromophores. Subsequent photoactivation of the chromophore leads to vibrational excitation of the complex and eventually to fragmentation of the peptide. Herein, the energetics that control the efficiency of this process are examined as a function of the characteristics of both the peptide and the noncovalently attached chromophore. Fragmentation efficiency decreases with increasing peptide size and is also constrained by the binding energy of the noncovalent adduct. The optimum chromophore should have excellent absorption at the excitation wavelength and a low luminescence quantum yield. It is demonstrated that a naphthyl based 18-crown-6 adduct is ideally suited for attaching to a variety peptides and fragmenting them following absorption of 266 nm light. [7][8][9][10][11]. Though none of these techniques is perfect, each has characteristic strengths and weaknesses. For example CID is easily employed in the source region of any instrument with atmospheric pressure ionization. CID is also easily accommodated elsewhere in an instrument as long as high vacuum is not required. In contrast, IRMPD is well suited for collisionless environments. In this regard, CID and IRMPD provide complementary capabilities. Furthermore, since both methods fragment ions by the stepwise addition of small amounts of energy, the results obtained are frequently quite similar.However, CID and IRMPD are both limited by the fact that energy deposition occurs over a relatively long time scale, typically milliseconds to seconds. In contrast, ultraviolet photodissociation (UVPD) occurs on a much shorter time scale and can yield fragment ions characteristic of CID or IRMPD. However, the major limitation of UVPD is that the precursor ion must contain a suitable chromophore. For peptides, UVPD requires either short wavelength lasers (less than 200 nm) or peptides rich in tyrosine, tryptophan, and phenylalanine that can absorb at longer wavelengths. Therefore, UVPD is either limited to a small subset of all peptides or constrained by undesirable technical challenges which are encountered when working in the vacuum ultraviolet. Thus, widespread implementation of UVPD for peptide fragmentation has been to date somewhat limited.However, Brodbelt and coworkers have recently described a method to circumvent the requirement for aromatic residues or short wavelength lasers [12]. In this work, a noncovalently attached chromophore was used to absorb energy from a photon and transfer it to a peptide, causing the peptide to fragment. 18-crown-6 ether (18C6), which preferentially associates with lysine residues via the formation of three hydrogen bonds, was used for...

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“…The fragmentation of peptides has been intensively inves-tigated in the past using various activation methods such as black-body radiation 11 , infrared multi-photon excitation 12 , ultraviolet 13 and vacuum ultraviolet 14 excitation, and collisions with gas-phase molecules or surfaces 15,16 . These measurements typically display cleavage of the weak peptide bond as a consequence of statistical fragmentation where the internal energy is randomized before dissociation occurs.…”

Section: Introductionmentioning

confidence: 99%

Selectivity in fragmentation of N-methylacetamide after resonant K-shell excitation

Salén

Kamińska

Squibb

et al. 2014

Phys. Chem. Chem. Phys.

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PostprintThis is the accepted version of a paper published in Physical Chemistry, Chemical Physics -PCCP. This paper has been peer-reviewed but does not include the final publisher proof-corrections or journal pagination.Citation for the original published paper (version of record):Salen, P., Kaminska, M., Squibb, R J., Richter, R., Alagia, M. et al. (2014) Selectivity in fragmentation of N-methylacetamide after resonant K-shell excitation. The fragmentation pattern of the peptide model system, N-methylacetamide, is investigated using ion time-of-flight (TOF) spectroscopy after resonant K-shell excitation. Corresponding near-edge X-ray absorption fine structure (NEXAFS) spectra recorded at high resolution at the C1s, N1s and O1s edges are presented. Analysis of the ion TOF data reveals a multitude of fragmentation channels and dissociation pathways. Comparison between the excitation of six different resonances in the vicinity of the C1s, N1s and O1s edges suggests evidence for site-selective bond breaking. In particular the breaking of the peptide bond and the N-C α bond show a clear correlation with resonant excitation at the N1s edge. Also, stronger tendencies towards site-selective bond breaking are found for the generation of single ions compared with ion pairs. Analysis of angular distributions of ions from breakage of the peptide bond yields a fragmentation time of < 400 fs.

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Fragmentation of Singly Charged Peptide Ions by Photodissociation at λ=157 nm

Cited by 148 publications

References 23 publications

Tracking radical migration in large hydrogen deficient peptides with covalent labels: Facile movement does not equal indiscriminate fragmentation

Tracking radical migration in large hydrogen deficient peptides with covalent labels: Facile movement does not equal indiscriminate fragmentation

Rapid peptide fragmentation without electrons, collisions, infrared radiation, or native chromophores

Selectivity in fragmentation of N-methylacetamide after resonant K-shell excitation

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