Non‐Covalent Interactions of a Neuroprotective Peptide Revealed by Photodissociative Cross‐Linking in the Gas Phase

Liu, Yang; Ramey, Zachary; Tureček, František

doi:10.1002/chem.201802174

Cited by 10 publications

(18 citation statements)

References 18 publications

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“…The resulting noncovalent complexes and photochemical products were analyzed using nano-ESI MS, which has the advantage of preserving noncovalent complexes. , A hybrid quadrupole time-of-flight mass spectrometer (q-TOF-MS, Maxis Impact, Bruker Daltonics, Bremen, Germany) was used for analysis . The MS/MS was performed for structural investigations by introducing nitrogen into the collision cell for CID of mass-selected complexes and reaction product ions.…”

Section: Methodsmentioning

confidence: 99%

Visible-Light-Driven [2 + 2] Photocycloadditions between Benzophenone and C═C Bonds in Unsaturated Lipids

Cao

et al. 2020

J. Am. Chem. Soc.

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The [2 + 2] photocycloaddition of alkenes and carbonyls is of fundamental interest and practical importance, as this process is extensively involved in oxetane-ring constructions. Although individual carbonyl group or alkene moiety has been utilized as photoactive species for oxetane formations upon ultraviolet photoexcitation, direct excitation of the entire noncovalent complex involving alkene and carbonyl substrates to achieve [2 + 2] photocycloadditions is rarely addressed. Herein, complexes with noncovalent interactions between benzophenone and CC bonds in unsaturated lipids have been successfully characterized, and for the first time a [2 + 2] cycloaddition leading to the formation of oxetanes has been identified under visible-light irradiation. The mechanism of this reaction is distinctly different from the well-studied Paternò–Büchi reaction. The entire complexes characterized as dimeric proton-bonded alkene and carbonyl substrates can be excited under visible light, leading to electron transfer from the alkene moiety in fatty acyls to the carbonyl group within the complex. These results provide new insight into utilizing noncovalent complexes for the synthesis of oxetanes in which the excitation wavelength becomes independent of each individual substrate.

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Section: Methodsmentioning

confidence: 99%

Visible-Light-Driven [2 + 2] Photocycloadditions between Benzophenone and C═C Bonds in Unsaturated Lipids

Cao

et al. 2020

J. Am. Chem. Soc.

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“…The integrated relative intensities of these complex ions, (SL + H) + : (SL* + H) + : (SL**) + = 42:48:10 indicated similar affinities to peptide S of natural l -adrenaline compared to that of L*. The d -adrenaline complexes furnished a (SD + H) + : (SD* + H) + : (SD**) + ratio of integrated ion intensities equal to 51:46:3, slightly preferring natural d -adrenaline binding to peptide S. Overall, the results indicated that, compared to peptide–peptide noncovalent complexes, − both the natural and tagged l - and d -adrenalines showed significant binding to peptide S upon electrospray ionization.…”

Section: Resultsmentioning

confidence: 79%

“…We were inspired by this finding, as well as by the previous gas-phase spectroscopic study, to design gas-phase adrenaline–peptide complexes for structure elucidation by a combination of UV photodissociation cross-linking (UVPD-X) and ion mobility mass spectrometry (IMMS). UVPD-X has been developed for structure analysis of noncovalent peptide–peptide − and peptide–oligonucleotide complexes, relying on chromophore-selective photodissociation of diazirine-tagged noncovalent complexes produced in the gas phase by electrospray ionization (Scheme ).…”

Section: Introductionmentioning

confidence: 99%

Probing d- and l-Adrenaline Binding to β₂-Adrenoreceptor Peptide Motifs by Gas-Phase Photodissociation Cross-Linking and Ion Mobility Mass Spectrometry

Liu

Nytka

et al. 2021

J. Am. Soc. Mass Spectrom.

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Diazirine-tagged D-and L-adrenaline derivatives formed abundant noncovalent gas-phase ion complexes with peptides N-Ac-SSIVSFY-NH 2 (peptide S) and N-Ac-VYILLNW-IGY-NH 2 (peptide V) upon electrospray ionization. These peptide sequences represent the binding motifs in the β 2 -adrenoreceptor. The structures of the gas-phase complexes were investigated by selective laser photodissociation of the diazirine chromophore at 354 nm, which resulted in a loss of N 2 and formation of a transient carbene intermediate in the adrenaline ligand without causing its expulsion. The photolyzed complexes were analyzed by collisioninduced dissociation (CID-MS 3 and CID-MS 4 ) in an attempt to detect cross-links and establish the binding sites. However, no cross-linking was detected in the complexes regardless of the peptide and D-or L-configuration in adrenaline. Cyclic ion mobility measurements were used to obtain collision cross sections (CCS) in N 2 for the peptide S complexes. These showed identical values, 334 ± 0.9 Å 2 , for complexes of the L-and D-adrenaline derivatives, respectively. Identical CCS were also obtained for peptide S complexes with natural L-and D-adrenaline, 317 ± 1.2 Å 2 , respectively. Born−Oppenheimer molecular dynamics (BOMD) in combination with full geometry optimization by density functional theory calculations provided structures for the complexes that were used to calculate theoretical CCS with the ion trajectory method. A close match (337 Å 2 ) was found for a single low Gibbs energy structure that displayed a binding pocket with Ser 2 and Ser 5 residues forming hydrogen bonds to the adrenaline catechol hydroxyls. Analysis of the BOMD trajectories revealed a small number of contacts between the incipient carbene carbon atom in the ligand and X−H bonds in the peptide, which was consistent with the lack of cross-linking. Temperature dependence of the internal dynamics of peptide S-adrenaline complexes as well as the specifics of the adrenaline carbene reactions are discussed. In particular, peptide amide hydrogen transfer to the carbene carbon atom was calculated to require crossing a potential energy barrier, which may hamper cross-linking in competition with carbene internal rearrangements.

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“…Enrichment and digestion of modified peptides enables low protein concentrations to be used, minimising the possibility of aggregation or other aberrant interactions. Additionally, the custom UV LED platform enables PI‐XL on a 10 second timescale, not possible with arc‐based lamps, and only previously achieved using pulsed lasers in solution or in the gas phase . The low cost (≈$300) and simplicity of our UV LED system makes these timescales accessible to any researcher.…”

Section: Figurementioning

confidence: 99%

Rapid Mapping of Protein Interactions Using Tag‐Transfer Photocrosslinkers

et al. 2018

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Analysing protein complexes by chemical crosslinking‐mass spectrometry (XL‐MS) is limited by the side‐chain reactivities and sizes of available crosslinkers, their slow reaction rates, and difficulties in crosslink enrichment, especially for rare, transient or dynamic complexes. Here we describe two new XL reagents that incorporate a methanethiosulfonate (MTS) group to label a reactive cysteine introduced into the bait protein, and a residue‐unbiased diazirine‐based photoactivatable XL group to trap its interacting partner(s). Reductive removal of the bait transfers a thiol‐containing fragment of the crosslinking reagent onto the target that can be alkylated and located by MS sequencing and exploited for enrichment, enabling the detection of low abundance crosslinks. Using these reagents and a bespoke UV LED irradiation platform, we show that maximum crosslinking yield is achieved within 10 seconds. The utility of this “tag and transfer” approach is demonstrated using a well‐defined peptide/protein regulatory interaction (BID80‐102/MCL‐1), and the dynamic interaction interface of a chaperone/substrate complex (Skp/OmpA).

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Non‐Covalent Interactions of a Neuroprotective Peptide Revealed by Photodissociative Cross‐Linking in the Gas Phase

Cited by 10 publications

References 18 publications

Visible-Light-Driven [2 + 2] Photocycloadditions between Benzophenone and C═C Bonds in Unsaturated Lipids

Visible-Light-Driven [2 + 2] Photocycloadditions between Benzophenone and C═C Bonds in Unsaturated Lipids

Probing d- and l-Adrenaline Binding to β₂-Adrenoreceptor Peptide Motifs by Gas-Phase Photodissociation Cross-Linking and Ion Mobility Mass Spectrometry

Rapid Mapping of Protein Interactions Using Tag‐Transfer Photocrosslinkers

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Non‐Covalent Interactions of a Neuroprotective Peptide Revealed by Photodissociative Cross‐Linking in the Gas Phase

Cited by 10 publications

References 18 publications

Visible-Light-Driven [2 + 2] Photocycloadditions between Benzophenone and C═C Bonds in Unsaturated Lipids

Visible-Light-Driven [2 + 2] Photocycloadditions between Benzophenone and C═C Bonds in Unsaturated Lipids

Probing d- and l-Adrenaline Binding to β2-Adrenoreceptor Peptide Motifs by Gas-Phase Photodissociation Cross-Linking and Ion Mobility Mass Spectrometry

Rapid Mapping of Protein Interactions Using Tag‐Transfer Photocrosslinkers

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Product

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Probing d- and l-Adrenaline Binding to β₂-Adrenoreceptor Peptide Motifs by Gas-Phase Photodissociation Cross-Linking and Ion Mobility Mass Spectrometry