The Mechanism Behind Top-Down UVPD Experiments: Making Sense of Apparent Contradictions

Julian, Ryan R.

doi:10.1007/s13361-017-1721-0

Cited by 82 publications

(106 citation statements)

References 36 publications

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“…It is also possible that fragment ions rearrange into a stable conformation on a timescale faster than we are able to measure. Further to this, some reports have indicated that lack of a specific UVPD fragment does not necessarily indicate strong non-covalent associations and suggests a combination of direct dissociation coupled with internal conversion (CID like) events [ 70 , 71 ] however in ECD experiments it is well-established that lack of fragments correlates with strong non-covalent associations [ 24 , 25 , 36 , 72 ]. For ubiquitin, as shown above, and as shall be shown for cytochrome c and myoglobin (below), we can interpret the UV-induced fragments in terms of regions of the proteins that are less encumbered by non-covalent associations.…”

Section: Resultsmentioning

confidence: 99%

Initial Protein Unfolding Events in Ubiquitin, Cytochrome c and Myoglobin Are Revealed with the Use of 213 nm UVPD Coupled to IM-MS

Theisen

Black

Corinti

et al. 2018

J. Am. Soc. Mass Spectrom.

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The initial stages of protein unfolding may reflect the stability of the entire fold and can also reveal which parts of a protein can be perturbed, without restructuring the rest. In this work, we couple UVPD with activated ion mobility mass spectrometry to measure how three model proteins start to unfold. Ubiquitin, cytochrome c and myoglobin ions produced via nESI from salty solutions are subjected to UV irradiation pre-mobility separation; experiments are conducted with a range of source conditions which alter the conformation of the precursor ion as shown by the drift time profiles. For all three proteins, the compact structures result in less fragmentation than more extended structures which emerge following progressive in-source activation. Cleavage sites are found to differ between conformational ensembles, for example, for the dominant charge state of cytochrome c [M + 7H], cleavage at Phe10, Thr19 and Val20 was only observed in activating conditions whilst cleavage at Ala43 is dramatically enhanced. Mapping the photo-cleaved fragments onto crystallographic structures provides insight into the local structural changes that occur as protein unfolding progresses, which is coupled to global restructuring observed in the drift time profiles. Graphical Abstract.

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Section: Resultsmentioning

confidence: 99%

Initial Protein Unfolding Events in Ubiquitin, Cytochrome c and Myoglobin Are Revealed with the Use of 213 nm UVPD Coupled to IM-MS

Theisen

Black

Corinti

et al. 2018

J. Am. Soc. Mass Spectrom.

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“…The low energy structures of [Leu-Enk + H] + are dominated by interactions of the -NH 3 + group with surrounding carbonyls. 10,19 This interaction can be significantly reduced by complexing the molecule with a 18-crown-6 molecule (CE), which has a high affinity towards protonated amines 27 and is expected to coordinate with the -NH 3 + group. Due to steric constraints, the CE solvated -NH 3 + group will not be able to interact strongly with other groups.…”

Section: Ir Spectroscopy Of [Leu-enk + Ce + H] + and [Leu-enk D + Ce mentioning

confidence: 99%

IR spectroscopy of protonated leu-enkephalin and its 18-crown-6 complex embedded in helium droplets

Flórez

Ahn

Gewinner

et al. 2015

Phys. Chem. Chem. Phys.

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Ultracold IR spectra of the protonated five amino acid peptide leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) embedded in superfluid helium droplets have been recorded using a free-electron laser as radiation source. The results show resolved spectra, which are in good agreement with theoretical calculations, as well as with the available gas-phase data indicating that the helium environment does not induce a significant matrix-shift. In addition, the effect of the interaction between the charge and the peptide backbone has been further investigated by complexing protonated leu-enkephalin with one 18-crown-6 molecule. Good agreement between the experimental and theoretical results allow for an assignment of a preferred molecular structure.

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“…7 This possibility has prompted many studies of CEs with peptides and proteins. 8,9 The utilization of CEs in medical applications is emerging. 10,11 For example, amino-crown ethers have been utilized for the delivery of 5-fluorouracil (5-FU), an anticancer agent used for the treatment of metastatic carcinomas of pancreas and breast.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and supramolecular assembly of fluorinated biogenic amine recognition host polymers

et al. 2019

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Copolymers containing hydroxyl (i.e. vinyl alcohol, VA) or fluorine functionalities are synthetic macromolecules having prominent biomedical applications. The concentration of hydroxyl groups along the polymer chain controls the polymer polarity. Moreover, the introduction of perfluorinated organic moieties via the OH functionalities may lead to macromolecules having potential magnetic resonance imaging (MRI) active properties. The ring-opening metathesis polymerization (ROMP) reaction using welldefined ruthenium-catalyzed systems is one of the most promising synthetic tools to fabricate such polymers. Co-polymerization of norbornene grafted pyridino-18-crown-6 ether (7) with fluorine-functionalized norbornenes (10 and 11) results in polymers bearing host molecular moieties. It has been demonstrated that the complexation of these host copolymers with biogenic amines including dopamine hydrochloride (12) and L-alanyl-L-lysine dipeptide hydrochloride (13) is straightforward. Based on the 1 H NMR investigation of the 7 and 12 complexation, an equilibrium constant of log K = 4.3 ± 0.6 could be calculated. The in situ 1 H NMR investigations have revealed that the complex formation of 13 with monomer 7 and perfluorinated copolymer cp-7-10 takes place via both the lysine -NH 3 + and the alanine -NH 3 + moieties. However, in the case of homopolymer poly-7, the lysine-NH 3 + group coordination was observed exclusively. According to theoretical calculations, molecular switching of the crown ether structure of both the 7 monomer and its cp-7-10 copolymer were observed from 90 degrees bent to planar structure upon -NH 3 + ion coordination. † Electronic supplementary information (ESI) available. See

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The Mechanism Behind Top-Down UVPD Experiments: Making Sense of Apparent Contradictions

Cited by 82 publications

References 36 publications

Initial Protein Unfolding Events in Ubiquitin, Cytochrome c and Myoglobin Are Revealed with the Use of 213 nm UVPD Coupled to IM-MS

Initial Protein Unfolding Events in Ubiquitin, Cytochrome c and Myoglobin Are Revealed with the Use of 213 nm UVPD Coupled to IM-MS

IR spectroscopy of protonated leu-enkephalin and its 18-crown-6 complex embedded in helium droplets

Synthesis and supramolecular assembly of fluorinated biogenic amine recognition host polymers

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