PXD038770

PXD038770 is an original dataset announced via ProteomeXchange.

Title	Cysteine Modification of Peptides and Proteins by Virtue of Highly Chemo-, Regio- and Stereoselective Hydrosulfuration of Ynamide
Description	Chemoselective modification of peptides and proteins has wide applications in chemical biology and pharmaceutical development. A highly efficient chemo-, regio- and stereoselective hydrosulfuration of ynamide was developed by taking advantage of an unprecedented β-addition of the thiols. Importantly, this reaction has been identified as an effective tool for Cys modification of peptides and proteins. The rationally designed strong electron-withdrawing triflyl group on the nitrogen atom of ynamides played a crucial role for controlling the chemo-, regio- and stereoselectivities while another substituent offered a handle for functionality diversification. This Cys modification strategy proceeded efficiently in a slightly basic aqueous conditions (pH 8) to provide exclusively the Z-isomer of the corresponding conjugates with superior stability. All the reactive peptide side chain functional groups such as amino, carboxyl, primary amide, and hydroxyl groups, as well as the unprotected imidazole and indole NH are compatible. This method displayed a broad substrate scope including linear and cyclic peptides, proteins and antibody. The potential application of this method in peptide and protein chemical biology was further exemplified by Cys-bioconjugation with ynamides containing functional molecules including small molecule drugs, fluorescent and affinity tags. In addition, this strategy was also compatible with click chemistry (performed in one-pot), which remarkably extended the application of this tool. Furthermore, the chemoselective biotinylation of ubiquitin(G47C) variant with a biotinylated ynamide, as well as the regioselective modification of Cys14 and Cys38 in bovine pancreatic trypsin inhibitor (BPTI), Cys34 of BSA and the antibody (Trastuzumab), could be accomplished readily under the optimized reaction conditions without perturbation of the other disulfide bonds. This method offered a novel and robust platform for Cys modification and opened new horizons for the production of peptide/protein/antibody-drug conjugates.
HostingRepository	PRIDE
AnnounceDate	2024-09-25
AnnouncementXML	Submission_2024-09-25_10:14:11.541.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rosi Fassler
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-12 22:52:10	ID requested
⏵ 1	2024-09-25 10:14:11	announced

10.1021/ACSCENTSCI.4C01148;

submitter keyword: LC-MS/MS, iodoacetamide, modifications, Ynamide, cysteine modification

Prof. Dana Reichmann
contact affiliation	Associate Professor, Vice president of the ISBMB society The Center for Nanoscience and Nanotechnology The Alexander Silberman Institute of Life Science Dept. of Biological Chemistry, room 1-637 The Hebrew University of Jerusalem Givat Ram Campus, Jerusalem, 9190401, Israel
contact email	danare@mail.huji.ac.il
lab head
Rosi Fassler
contact affiliation	Hebrew University of Jerusalem
contact email	rosi.fassler@mail.huji.ac.il
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/2024/09/PXD038770

PRIDE project URI

• PRIDE
  1. PXD038770
     1. Label: PRIDE project
     2. Name: Cysteine Modification of Peptides and Proteins by Virtue of Highly Chemo-, Regio- and Stereoselective Hydrosulfuration of Ynamide