PXD038723

PXD038723 is an original dataset announced via ProteomeXchange.

Title	Chemoselective umpolung of thiols to episulfoniums for cysteine bioconjugation
Description	Modification of native cysteine is an important tool in protein research and relies on fast and chemoselective reactions under bioambient conditions. Nucleophilic cysteine can be functionalized with electrophiles, such as maleimides, that carry specific chemical groups, depending on the desired application. However, each modification requires the synthesis of a different reagent. Cysteine can also be modified into an electrophile itself, for example by elimination to form the Michael acceptor dehydroalanine, for subsequent functionalization with select nucleophiles in a second, independent step. Herein, we report the first bioconjugation strategy that transforms cysteine into a highly reactive electrophilic intermediate in situ to enable conjugation with a broader and diverse set of bioorthogonal nucleophiles in a single step. In contrast to all previous methods, vinyl-thianthrenium salts chemoselectively transform cysteine into a versatile episulfonium intermediate, even in the presence of other nucleophiles. One-step bioconjugation with various nucleophiles is therefore possible with a single reagent. The unique reactivity profile enabled by umpolung of cysteine links nucleophiles and biomolecules through a short and stable ethylene linker, only two atoms remote from the cysteine sulfur atom, ideal for introduction of IR labels, post-translational-modifications, or NMR probes. In the absence of exogenous nucleophiles, nucleophilic amino acids can react with the episulfonium intermediates, which provides a method for native peptide stapling and macrocyclization. Ready synthetic access to different isotopologues of vinyl-thianthrenium enables additional applications in quantitative proteomics.
HostingRepository	jPOST
AnnounceDate	2023-12-20
AnnouncementXML	Submission_2024-01-08_00:42:37.005.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jürgen Eirich
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	unknown modification
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-09 08:16:57	ID requested
1	2023-12-19 07:00:08	announced
⏵ 2	2024-01-08 00:42:37	announced	2024-01-08: Updated PubMed.

Hartmann P, Bohdan K, Hommrich M, Juli, á F, Vogelsang L, Eirich J, Zangl R, Far, è, s C, Jacobs JB, Mukhopadhyay D, Mengeler JM, Vetere A, Sterling MS, Hinrichs H, Becker S, Morgner N, Schrader W, Finkemeier I, Dietz KJ, Griesinger C, Ritter T, Chemoselective umpolung of thiols to episulfoniums for cysteine bioconjugation. Nat Chem, 16(3):380-388(2024) [pubmed]

submitter keyword: cysteine labeling, chemical proteomics

Iris Finkemeier
lab head
Jürgen Eirich
contact affiliation	University of Münster - WWU - Institute for Biology and Biotechnology of Plants
dataset submitter

jPOST dataset URI

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