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Article: Reduction of pentavalent antimony by trypanothione and formation of a binary and ternary complex of antimony(III) and trypanothione

TitleReduction of pentavalent antimony by trypanothione and formation of a binary and ternary complex of antimony(III) and trypanothione
Authors
KeywordsAntimony
Electrospary ionization mass spectrometry
Nuclear magnetic resonance spectroscopy
Reduction
Trypanothione
Issue Date2003
PublisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00775/index.htm
Citation
Journal Of Biological Inorganic Chemistry, 2003, v. 8 n. 6, p. 689-697 How to Cite?
AbstractSeveral pentavalent antimony compounds have been used for the treatment of leishmaniasis for decades. However, the mechanism of these antimony drugs still remains unclear. One of their targets is thought to be trypanothione, a major low molecular mass thiol inside the parasite. We show that pentavalent antimony (Sb v) can be rapidly reduced to its trivalent state by trypanothione at mildly acidic conditions and 310 K (k = 4.42 M -1 min -1 at pH 6.4), and that Sb III can be bound to trypanothione to form an Sb III-trypanothione complex. NMR data demonstrate that Sb III binds to trypanothione at the two thiolates of the cysteine residues, and that the binding is pH dependent and is strongest at biological pH with a stability constant logK = 23.6 at 298 K (0.1 M NaNO 3). The addition of low molecular monothiol ligands such as glutathione and cysteine to the Sb III-trypanothione complex results in the formation of a ternary complex. Thiolates from both trypanothione and monothiol bind to the Sb III center. The formation of the ternary complex is important, as the antileishmanial properties of the drugs are probably due to a complex between of Sb III-trypanothione and enzymes. Although thermodynamically stable, the complex is kinetically labile and the free and bound forms of thiolates exchange on the 1H NMR timescale. Such a facile exchange may be crucial for the transport of Sb III within parasites.
Persistent Identifierhttp://hdl.handle.net/10722/69967
ISSN
2015 Impact Factor: 2.495
2015 SCImago Journal Rankings: 0.882
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYan, Sen_HK
dc.contributor.authorLi, Fen_HK
dc.contributor.authorDing, Ken_HK
dc.contributor.authorSun, Hen_HK
dc.date.accessioned2010-09-06T06:18:29Z-
dc.date.available2010-09-06T06:18:29Z-
dc.date.issued2003en_HK
dc.identifier.citationJournal Of Biological Inorganic Chemistry, 2003, v. 8 n. 6, p. 689-697en_HK
dc.identifier.issn0949-8257en_HK
dc.identifier.urihttp://hdl.handle.net/10722/69967-
dc.description.abstractSeveral pentavalent antimony compounds have been used for the treatment of leishmaniasis for decades. However, the mechanism of these antimony drugs still remains unclear. One of their targets is thought to be trypanothione, a major low molecular mass thiol inside the parasite. We show that pentavalent antimony (Sb v) can be rapidly reduced to its trivalent state by trypanothione at mildly acidic conditions and 310 K (k = 4.42 M -1 min -1 at pH 6.4), and that Sb III can be bound to trypanothione to form an Sb III-trypanothione complex. NMR data demonstrate that Sb III binds to trypanothione at the two thiolates of the cysteine residues, and that the binding is pH dependent and is strongest at biological pH with a stability constant logK = 23.6 at 298 K (0.1 M NaNO 3). The addition of low molecular monothiol ligands such as glutathione and cysteine to the Sb III-trypanothione complex results in the formation of a ternary complex. Thiolates from both trypanothione and monothiol bind to the Sb III center. The formation of the ternary complex is important, as the antileishmanial properties of the drugs are probably due to a complex between of Sb III-trypanothione and enzymes. Although thermodynamically stable, the complex is kinetically labile and the free and bound forms of thiolates exchange on the 1H NMR timescale. Such a facile exchange may be crucial for the transport of Sb III within parasites.en_HK
dc.languageengen_HK
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00775/index.htmen_HK
dc.relation.ispartofJournal of Biological Inorganic Chemistryen_HK
dc.subjectAntimonyen_HK
dc.subjectElectrospary ionization mass spectrometryen_HK
dc.subjectNuclear magnetic resonance spectroscopyen_HK
dc.subjectReductionen_HK
dc.subjectTrypanothioneen_HK
dc.titleReduction of pentavalent antimony by trypanothione and formation of a binary and ternary complex of antimony(III) and trypanothioneen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0949-8257&volume=8&spage=689&epage=697&date=2003&atitle=Reduction+of+pentavalent+antimony+by+trypanothione+and+formation+of+a+binary+and+ternary+complex+of+antimony(III)+and+trypanothione+en_HK
dc.identifier.emailSun, H:hsun@hkucc.hku.hken_HK
dc.identifier.authoritySun, H=rp00777en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s00775-003-0468-1en_HK
dc.identifier.pmid12827457-
dc.identifier.scopuseid_2-s2.0-0041654771en_HK
dc.identifier.hkuros161523en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0041654771&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume8en_HK
dc.identifier.issue6en_HK
dc.identifier.spage689en_HK
dc.identifier.epage697en_HK
dc.identifier.isiWOS:000184294700012-
dc.publisher.placeGermanyen_HK
dc.identifier.scopusauthoridYan, S=7401744858en_HK
dc.identifier.scopusauthoridLi, F=36079222200en_HK
dc.identifier.scopusauthoridDing, K=7103197872en_HK
dc.identifier.scopusauthoridSun, H=7404827446en_HK

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