File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: An anticancer gold(III)-activated porphyrin scaffold that covalently modifies protein cysteine thiols

TitleAn anticancer gold(III)-activated porphyrin scaffold that covalently modifies protein cysteine thiols
Authors
Keywordsgold
porphyrin
ligand reactivity
cysteine thiol conjugation
antitumor agents
Issue Date2020
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings of the National Academy of Sciences, 2020, v. 117 n. 3, p. 1321-1329 How to Cite?
AbstractCysteine thiols of many cancer-associated proteins are attractive targets of anticancer agents. Herein, we unequivocally demonstrate a distinct thiol-targeting property of gold(III) mesoporphyrin IX dimethyl ester (AuMesoIX) and its anticancer 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 anticancer 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 antitumor activity in mice. Our study has uncovered a gold(III)-induced ligand scaffold reactivity for thiol targeting that can be exploited for anticancer applications.
Persistent Identifierhttp://hdl.handle.net/10722/282889
ISSN
2020 Impact Factor: 11.205
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorTong, KC-
dc.contributor.authorLok, CN-
dc.contributor.authorWan, PK-
dc.contributor.authorHu, D-
dc.contributor.authorFung, YME-
dc.contributor.authorChang, XY-
dc.contributor.authorHuang, S-
dc.contributor.authorJiang, H-
dc.contributor.authorChe, CM-
dc.date.accessioned2020-06-05T06:22:45Z-
dc.date.available2020-06-05T06:22:45Z-
dc.date.issued2020-
dc.identifier.citationProceedings of the National Academy of Sciences, 2020, v. 117 n. 3, p. 1321-1329-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/282889-
dc.description.abstractCysteine thiols of many cancer-associated proteins are attractive targets of anticancer agents. Herein, we unequivocally demonstrate a distinct thiol-targeting property of gold(III) mesoporphyrin IX dimethyl ester (AuMesoIX) and its anticancer 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 anticancer 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 antitumor activity in mice. Our study has uncovered a gold(III)-induced ligand scaffold reactivity for thiol targeting that can be exploited for anticancer applications.-
dc.languageeng-
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org-
dc.relation.ispartofProceedings of the National Academy of Sciences-
dc.rightsProceedings of the National Academy of Sciences. Copyright © National Academy of Sciences.-
dc.subjectgold-
dc.subjectporphyrin-
dc.subjectligand reactivity-
dc.subjectcysteine thiol conjugation-
dc.subjectantitumor agents-
dc.titleAn anticancer gold(III)-activated porphyrin scaffold that covalently modifies protein cysteine thiols-
dc.typeArticle-
dc.identifier.emailTong, KC: kctong12@hku.hk-
dc.identifier.emailLok, CN: cnlok@hkucc.hku.hk-
dc.identifier.emailWan, PK: kiwanhk@hku.hk-
dc.identifier.emailHu, D: hudi@hku.hk-
dc.identifier.emailFung, YME: eva.fungym@hku.hk-
dc.identifier.emailChang, XY: xychang@hku.hk-
dc.identifier.emailChe, CM: chemhead@hku.hk-
dc.identifier.authorityLok, CN=rp00752-
dc.identifier.authorityFung, YME=rp01986-
dc.identifier.authorityChe, CM=rp00670-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.1915202117-
dc.identifier.pmid31896586-
dc.identifier.pmcidPMC6983449-
dc.identifier.scopuseid_2-s2.0-85078141574-
dc.identifier.hkuros310316-
dc.identifier.volume117-
dc.identifier.issue3-
dc.identifier.spage1321-
dc.identifier.epage1329-
dc.identifier.isiWOS:000508977600020-
dc.publisher.placeUnited States-
dc.identifier.issnl0027-8424-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats