Comparative thermal and thermodynamic study of DNA chemically modified with antitumor drug cisplatin and its inactive analog transplatin

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題名:	Comparative thermal and thermodynamic study of DNA chemically modified with antitumor drug cisplatin and its inactive analog transplatin
作者:	薛雅薇;Lando, Dmitri Y.;Chang, Chun-Ling;Fridman, Alexander S.;Grigoryan, Inessa E.;Galyuk, Elena N.;Hsueh, Ya-Wei;Hu, Chin-Kun
貢獻者:	理學院物理學系
關鍵詞:	Animals;Antineoplastic Agents - chemistry;Binding Sites;Cattle;Cisplatin - chemistry;DNA - chemistry;DNA Adducts - chemistry;DNA complexes with platinum compounds;DNA differential scanning calorimetry;DNA optical melting studies;Entropy;Humans;Neoplasms - chemistry;Neoplasms - metabolism;Nucleic Acid Conformation;Temperature;Thermodynamics
日期:	2014-01-01
上傳時間:	2026-04-23 11:48:29 (UTC+8)
出版者:	Elsevier Inc.;United States: Elsevier Inc
摘要:	摘要： Antitumor activity of cisplatin is exerted by covalent binding to DNA. For comparison, studies of cisplatin-DNA complexes often employ the very similar but inactive transplatin. In this work, thermal and thermodynamic properties of DNA complexes with these compounds were studied using differential scanning calorimetry (DSC) and computer modeling. DSC demonstrates that cisplatin decreases thermal stability (melting temperature, Tm) of long DNA, and transplatin increases it. At the same time, both compounds decrease the enthalpy and entropy of the helix–coil transition, and the impact of transplatin is much higher. From Pt/nucleotide molar ratio rb=0.001, both compounds destroy the fine structure of DSC profile and increase the temperature melting range (ΔT). For cisplatin and transplatin, the dependences δTm vs rb differ in sign, while δΔT vs rb are positive for both compounds. The change in the parameter δΔT vs rb demonstrates the GC specificity in the location of DNA distortions. Our experimental results and calculations show that 1) in contrast to [Pt(dien)Cl]Cl, monofunctional adducts formed by transplatin decrease the thermal stability of long DNA at [Na+]>30mM; 2) interstrand crosslinks of cisplatin and transplatin only slightly increase Tm; 3) the difference in thermal stability of DNA complexes with cisplatin vs DNA complexes with transplatin mainly arises from the different thermodynamic properties of their intrastrand crosslinks. This type of crosslink appears to be responsible for the antitumor activity of cisplatin. At any [Na+] from interval 10–210mM, cisplatin and transplatin intrastrand crosslinks give rise to destabilization and stabilization, respectively. Cisplatin and transplatin decrease enthalpy of DNA helix–coil transition by 26 and 38kcal/mol per modifications. The fine structure of melting profile disappears from Pt/nucleotide=0.001 to 0.05. In contrast to antitumor drug cisplatin, intrastrand crosslinks of inactive transplatin increase DNA thermal stability. Monofunctional adducts of transplatin decrease DNA thermal stability. [Display omitted] 其他題名： J Inorg Biochem 出版者： United States: Elsevier Inc 出版日期： 2014-08-01 出處： Journal of inorganic biochemistry, 2014-08, Vol.137, p.85-93 版權： 2014 Elsevier Inc. 版權： Copyright © 2014 Elsevier Inc. All rights reserved. 識別號： ISSN: 0162-0134 識別號： ISSN: 1873-3344 識別號： EISSN: 1873-3344 識別號： DOI: 10.1016/j.jinorgbio.2014.04.010 識別號： PMID: 24831492
顯示於類別:	[物理學系] 期刊論文

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