PXD016875-2

PXD016875 is an original dataset announced via ProteomeXchange.

Title	An Anti-Cancer Gold(III)-Activated Porphyrin Scaffold that Covalently Modifies Protein Cysteine Thiols
Description	Cysteine thiols of many cancer-associated proteins are attractive targets of anti-cancer agents. Herein, we unequivocally demonstrate a distinct thiol-targeting property of gold(III) mesoporphyrin IX dimethyl ester (AuMesoIX) and its anti-cancer activities. While the binding of cysteine thiols with metal complexes usually occurs via M–S bond formation, AuMesoIX is unique in that the meso-carbon atom of the porphyrin ring is activated by the gold(III) ion to undergo nucleophilic aromatic substitution with thiols. AuMesoIX was shown to modify reactive cysteine residues and inhibit the activities of anti-cancer protein targets including thioredoxin, peroxiredoxin, and deubiquitinases. Treatment of cancer cells with AuMesoIX resulted in the formation of gold-bound sulfur-rich protein aggregates, oxidative stress-mediated cytotoxicity, and accumulation of ubiquitinated proteins. Importantly, AuMesoIX exhibited effective anti-tumor activity in mice. Our study has uncovered a gold(III)-induced ligand scaffold reactivity for thiol targeting that can be exploited for anti-cancer applications.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:26:38.173.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Di HU
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2019-12-20 03:19:58	ID requested
1	2021-09-08 13:53:10	announced
⏵ 2	2024-10-22 05:26:46	announced	2024-10-22: Updated project metadata.

10.1073/pnas.1915202117;

Tong KC, Lok CN, Wan PK, Hu D, Fung YME, Chang XY, Huang S, Jiang H, Che CM, An anticancer gold(III)-activated porphyrin scaffold that covalently modifies protein cysteine thiols. Proc Natl Acad Sci U S A, 117(3):1321-1329(2020) [pubmed]

submitter keyword: Gold • Porphyrin • Ligand Reactivity• Cysteine Thiol Conjugation • Anti-tumor Agents

Chi-Ming Che
contact affiliation	State Key Laboratory of Synthetic Chemistry and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China
contact email	cmche@hku.hk
lab head
Di HU
contact affiliation	Department of Chemistry, The University of Hong Kong
contact email	hudi@hku.hk
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/2021/09/PXD016875

PRIDE project URI

• PRIDE
  1. PXD016875
     1. Label: PRIDE project
     2. Name: An Anti-Cancer Gold(III)-Activated Porphyrin Scaffold that Covalently Modifies Protein Cysteine Thiols