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Titolo:
Surprising reactions of iodo Pt(IV) and Pt(II) complexes with human albumin: Detection of Cys34 sulfenic acid
Autore:
Kratochwil, NA; Ivanov, AI; Patriarca, M; Parkinson, JA; Gouldsworthy, AM; Murdoch, PD; Sadler, PJ;
Indirizzi:
Univ Edinburgh, Dept Chem, Edinburgh EH9 3JJ, Midlothian, Scotland Univ Edinburgh Edinburgh Midlothian Scotland EH9 3JJ Midlothian, Scotland
Titolo Testata:
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
fascicolo: 36, volume: 121, anno: 1999,
pagine: 8193 - 8203
SICI:
0002-7863(19990915)121:36<8193:SROIPA>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
PLATINUM ANTICANCER DRUG; BINDING ACTIVITY INVITRO; HUMAN SERUM-ALBUMIN; X-RAY STRUCTURE; CRYSTAL-STRUCTURE; DNA-BINDING; REDOX REGULATION; REDUCTIVE ELIMINATION; ANGSTROM RESOLUTION; OXIDATIVE ADDITION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Physical, Chemical & Earth Sciences
Citazioni:
86
Recensione:
Indirizzi per estratti:
Indirizzo: Sadler, PJ Univ Edinburgh, Dept Chem, Kings Bldg,W Mains Rd, Edinburgh EH93JJ, Midlothian, Scotland Univ Edinburgh Kings Bldg,W Mains Rd Edinburgh Midlothian Scotland EH9 3JJ
Citazione:
N.A. Kratochwil et al., "Surprising reactions of iodo Pt(IV) and Pt(II) complexes with human albumin: Detection of Cys34 sulfenic acid", J AM CHEM S, 121(36), 1999, pp. 8193-8203

Abstract

cis-[PtCl2(NH3)(2)] is the anticancer drug cisplatin, but the iodide analogue cis-[PtI2(NH3)(2)] is inactive. This inactivity is usually attributed to the greater stability and lower reactivity of Pt-I bonds compared to Pt-Cl in aqueous solution. Interest in reactions of Pt(IV) complexes with thiols arises from the reductive activation of Pt(IV) anticancer drugs in blood plasma. Recently, we found (J. Am. Chem. Sec. 1998, 120, 8253-8254) that low M-r thiols react with Pt(IV)-I bonds of trans,cis-[Pt(en)(OH)(2)I-2] via attack on the coordinated iodo ligand giving rise to reactive chelate-ring-opened Pt(II) ethylenediamine species. Here we report reactions of the Pt(II) and Pt(IV) complexes [Pt(en)I-2] and trans,cis-[Pt(en)(OH)(2)I-2] With the major thiol in blood plasma, Cys34 of the protein albumin (66 kDa). Unexpectedly, [Pt(en)I-2] reacted more rapidly with albumin than the cisplatin analogue, [Pt(en)Cl-2], and did not give products with Pt bound to Cys34. The Pt(IV) chloro analogue, trans,cis-[Pt(en)(OH)(2)Cl-2], did not react at all with albumin. Reactions of trans,cis[Pt(en)(OH)(2)I-2] with the protein, via direct attack of an iodo ligand on Cys34, gave rise to a relatively stable sulfenic acid derivative, in contrast to reactions with low M-r thiols. Reactions of Pt complexes with thiols in proteins can therefore take a different course: albumin can exert control over the reactivity of Cys34 andstabilize activated derivatives such as the sulfenyl iodide and sulfenic acid. The reactivity of iodide ligands in Pt complexes is much higher than has been previously recognized, and it may be possible to incorporate them into drug design strategies.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 12:40:21