PXD033004

PXD033004 is an original dataset announced via ProteomeXchange.

Title	Ethynyl-1,2,3-triazolyl-phosphinate based electrophiles for cysteine labelling
Description	Herein we report the density functional theory (DFT) guided discovery of ethynyl-triazolyl-phosphinates (PT) as a new class of electrophilic warhead for cysteine selective bioconjugation. Using DFT-calculations, we found that both the electron withdrawing character as well as the π-acidity of the P-bound triazole significantly contribute to its enhanced reactivity towards thiols. We developed a straightforward synthetic route starting from readily available organic azides and diethynyl phosphinates using CuI-catalysed azide alkyne cycloaddition in aqueous buffer to access a variety of functional electrophiles. These reagents were used to obtain fluorescent peptide-conjugates for receptor labelling on live cells and in the generation of stable and biologically active antibody-drug-conjugates. Moreover, we were able to incorporate PT-electrophiles into azide-containing proteins under native conditions and demonstrate their potential in protein-protein conjugation. Finally, we showcase the excellent cysteine selectivity of this new class of electrophile in mass spectrometry based, proteome-wide cysteine profiling.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:39:05.967.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Stieger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-06 08:02:05	ID requested
1	2023-03-11 00:12:19	announced
⏵ 2	2023-11-14 08:39:09	announced	2023-11-14: Updated project metadata.

Stieger CE, Park Y, de Geus MAR, Kim D, Huhn C, Slenczka JS, Ochtrop P, M, ü, chler JM, S, ü, ssmuth RD, Broichhagen J, Baik MH, Hackenberger CPR, DFT-Guided Discovery of Ethynyl-Triazolyl-Phosphinates as Modular Electrophiles for Chemoselective Cysteine Bioconjugation and Profiling. Angew Chem Int Ed Engl, 61(41):e202205348(2022) [pubmed]

submitter keyword: protein cross-linking,Chemical Proteomics

Christian Hackenberger
contact affiliation	Chemical Biology Department, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany. Department of Chemistry, Humboldt Universität zu Berlin, Brook-Taylor-Straße 2, 12489 Berlin, Germany
contact email	hackenbe@fmp-berlin.de
lab head
Christian Stieger
contact affiliation	FMP Belrin
contact email	stieger@fmp-berlin.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/03/PXD033004

PRIDE project URI

• PRIDE
  1. PXD033004
     1. Label: PRIDE project
     2. Name: Ethynyl-1,2,3-triazolyl-phosphinate based electrophiles for cysteine labelling