Amino acid-linked platinum(II) compounds: non-canonical nucleoside preferences and influence on glycosidic bond stabilities
作者:Bett Kimutai、C. C. He、Andrew Roberts、Marcel L. Jones、Xun Bao、Jun Jiang、Zhihua Yang、M. T. Rodgers、Christine S. Chow
DOI:10.1007/s00775-019-01693-y
日期:2019.10
(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
摘要核糖核酸酶是药物结合并发挥其抗癌活性的理想靶标。顺铂(cisPt)优先协调DNA中的2'-脱氧鸟苷(dGuo)残基。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作为抗癌药取得了成功,但它仍然具有许多降低其功效的缺点,包括修复加合物和耐药性。解决此问题的一些方法涉及开发与其他嘌呤核苷碱基(包括在RNA中发现的那些)协调的化合物。在这项工作中,研究了丙氨酸和鸟氨酸(分别为AlaPt和OrnPt)的氨基酸连接的铂(II)(AAPt)化合物。它们对DNA和RNA嘌呤核苷的反应性偏好(即2'-脱氧腺苷(dAdo),确定了腺苷(Ado),dGuo和鸟苷(Guo)。所选化合物通过在嘌呤核苷碱基的N1,N3或N7位反应形成主要的单官能加合物。此外,探索了影响Ado残基的糖苷键稳定性的AAPt化合物的特征。对于AlaPt-Ado和OrnPt-Ado异构体,糖苷