Amino acid-linked platinum(II) compounds: non-canonical nucleoside preferences and influence on glycosidic bond stabilities
Amino acid-linked platinum(II) compounds: non-canonical nucleoside preferences and influence on glycosidic bond stabilities
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氨基酸连接的铂 (II) 化合物：非规范核苷偏好及其对糖苷键稳定性的影响
DOI：
10.1007/s00775-019-01693-y
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Chow, Christine S.
中科院分区：
文献类型：
--
作者：
Kimutai, Bett;He, C. C.;Roberts, Andrew;Jones, Marcel L.;Bao, Xun;Jiang, Jun;Yang, Zhihua;Rodgers, M. T.;Chow, Christine S.
摘要核碱基是药物结合和发挥抗癌作用的理想靶点。顺铂（cisPt）优先与DNA内的2 ' -脱氧鸟苷（dGuo）残基配合。形成的dGuo加合物改变了DNA结构，有助于抑制功能并最终导致癌细胞死亡。尽管cisPt作为一种抗癌药物取得了成功，但它也有一些缺点，包括对加合物的修复和耐药性，这些缺点降低了它的疗效。克服这一问题的一些方法涉及开发与其他嘌呤核碱基协调的化合物，包括在RNA中发现的嘌呤核碱基。本文研究了丙氨酸和鸟氨酸的氨基酸连接铂（II） （AAPt）化合物（分别为AlaPt和OrnPt）。测定了它们对DNA和RNA嘌呤核苷（即2 ' -脱氧腺苷（dAdo）、腺苷（Ado）、dGuo和鸟苷（Guo））的反应性偏好。所选择的化合物主要通过在嘌呤核碱基的N1、N3或N7位置反应形成单功能加合物。此外，还探讨了影响Ado残基糖苷键稳定性的AAPt化合物的特征。AlaPt-Ado和OrnPt-Ado异构体的糖苷键裂解激活方式不同。在非规范残基上形成独特的加合物和随后的糖苷键的不稳定是可以规避铂基耐药的重要特征。图形抽象
AbstractNucleobases serve as ideal targets where drugs bind and exert their anticancer activities. Cisplatin (cisPt) preferentially coordinates to 2′-deoxyguanosine (dGuo) residues within DNA. The dGuo adducts that are formed alter the DNA structure, contributing to inhibition of function and ultimately cancer cell death. Despite its success as an anticancer drug, cisPt has a number of drawbacks that reduce its efficacy, including repair of adducts and drug resistance. Some approaches to overcome this problem involve development of compounds that coordinate to other purine nucleobases, including those found in RNA. In this work, amino acid-linked platinum(II) (AAPt) compounds of alanine and ornithine (AlaPt and OrnPt, respectively) were studied. Their reactivity preferences for DNA and RNA purine nucleosides (i.e., 2′-deoxyadenosine (dAdo), adenosine (Ado), dGuo, and guanosine (Guo)) were determined. The chosen compounds form predominantly monofunctional adducts by reacting at the N1, N3, or N7 positions of purine nucleobases. In addition, features of AAPt compounds that impact the glycosidic bond stability of Ado residues were explored. The glycosidic bond cleavage is activated differentially for AlaPt-Ado and OrnPt-Ado isomers. Formation of unique adducts at non-canonical residues and subsequent destabilization of the glycosidic bonds are important features that could circumvent platinum-based drug resistance.Graphic abstract
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钠阳离子化与质子化对钠阳离子化 Urd 和 dUrd 的构象和 N-糖苷键稳定性的影响：[Urd Na] 的溶液构象在 ESI 上得以保留。
DOI：
--
发表时间：
2017
期刊：
Physical Chemistry, Chemical Physics - PCCP
影响因子：
--
作者：
Y. Zhu;H. Roy;N. A. Cunningham;S. Strobehn;J. Gao;M. U. Munshi;G. Berden;J. Oomens;M. Rodgers
通讯作者：
M. Rodgers
影响因子：
4.7
作者：
A. S. Prakash;N. Gibson
通讯作者：
A. S. Prakash;N. Gibson
影响因子：
15
作者：
Mantri, Yogita;Lippard, Stephen J.;Baik, Mu-Hyun
通讯作者：
Baik, Mu-Hyun
影响因子：
2.8
作者：
May, Kerrie L.;Yan, Qing;Tumer, Nilgun E.
通讯作者：
Tumer, Nilgun E.
铂化合物与含有鸟嘌呤和胞嘧啶的短寡脱氧核苷酸的相互作用。
DOI：
10.1111/j.1432-1033.1983.tb07660.x
发表时间：
1983
期刊：
European journal of biochemistry
影响因子：
--
作者：
A. Marcelis;J. H. J. D. Hartog;G. A. V. Marel;Gerry Wille;J. Reedijk
通讯作者：
J. Reedijk