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Titolo:
Steric control of stereoselective interactions between the platinum(II) complex [PtCl2(1,4-diazacycloheptane)] and DNA: comparison with cis-[PtCl2(NH3)(2)] and [PtCl2(ethane-1,2-diamine)] using DNA binding and molecular modeling studies
Autore:
Hambley, TW; Ling, ECH; Munk, VP; Davies, MS;
Indirizzi:
Univ Sydney, Sch Chem, Ctr Heavy Met Res, Sydney, NSW 2006, Australia UnivSydney Sydney NSW Australia 2006 et Res, Sydney, NSW 2006, Australia
Titolo Testata:
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
fascicolo: 5-6, volume: 6, anno: 2001,
pagine: 534 - 542
SICI:
0949-8257(200106)6:5-6<534:SCOSIB>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTITUMOR DRUG CIS-DIAMMINEDICHLOROPLATINUM(II); INTERSTRAND CROSS-LINKS; RNA-POLYMERASES; STRANDED OLIGONUCLEOTIDES; SEQUENCE SPECIFICITY; MECHANICS ANALYSIS; A-DNA; ADDUCTS; CISPLATIN; PLATINATION;
Keywords:
platinum; anticancer; DNA binding; stereoselectivity; steric interactions;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Hambley, TW Univ Sydney, Sch Chem, Ctr Heavy Met Res, Sydney, NSW 2006, Australia Univ Sydney Sydney NSW Australia 2006 ey, NSW 2006, Australia
Citazione:
T.W. Hambley et al., "Steric control of stereoselective interactions between the platinum(II) complex [PtCl2(1,4-diazacycloheptane)] and DNA: comparison with cis-[PtCl2(NH3)(2)] and [PtCl2(ethane-1,2-diamine)] using DNA binding and molecular modeling studies", J BIOL I CH, 6(5-6), 2001, pp. 534-542

Abstract

The rate and extent of binding of [PtCl2(hpip)] (hpip =homopiperazine=1,4-diazacycloheptane) and CiS-[PtCl2(NH3)(2)] to calf thymus DNA was measured using atomic absorption spectroscopy and it was found that [PtCl2(hpip)] bound both more rapidly and to a greater extent than did cis-[PtCl2(NH3)(2)]. The binding of [PtCl2(hpip)] and [PtCl2(en)] (en=ethane-1,2-diamine) to salmon sperm DNA and to synthetic, self-complementary 10-base-pair and 52-base-pair oligonucleotides was studied using enzymatic digestion and HPLC analysis of the products. [PtCl2(hpip)] forms approximately two-fold fewer GpG and ApG intrastrand adducts and concomitantly more monofunctional adducts than does [PtCl2(en)]. In the case of [PtCl2(hpip)], two GpG adducts, corresponding to the different orientations of the hpip ligand with respect to the DNA, were observed in a 1:3.3 ratio. The minor product corresponds to theorientation in which the bulkier propylene chain of the hpip ligand is adjacent to, and makes close contacts with, the floor of the major groove. When the reaction was repeated with a synthetic oligonucleotide decamer duplex, the ratio of the two forms was approximately 1:1.9 and with the 52-mer duplex it was 1:2.4, revealing an apparent systematic dependence of stereoselectivity on nucleotide size. Computer modeling of the two adducts formed by[PtCl2(hpip)] and those formed by [PtCl2(en)] and cis-[PtCl2(NH3)(2)] revealed that non-bonded interactions between the hpip ligand and the DNA were probably responsible for both the decreased proportion of GpG adducts formed by [PtCl2(hpip)] and the stereoselectivity exhibited in the formation of these adducts. This is the first case in which the stereoselectivity can beascribed to steric factors alone.

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Documento generato il 30/09/20 alle ore 03:48:04