Department of Chemistry, University of Turku, Vatselankatu 2, 20014 Turku, Finland.
Int J Mol Sci. 2018 May 28;19(6):1588. doi: 10.3390/ijms19061588.
Short oligonucleotides with cyclopalladated benzylamine moieties at their 5'-termini have been prepared to test the possibility of conferring palladacyclic anticancer agents sequence-selectivity by conjugation with a guiding oligonucleotide. Hybridization of these oligonucleotides with natural counterparts was studied by UV and CD (circular dichroism) melting experiments in the absence and presence of a competing ligand (2-mercaptoethanol). Cyclopalladated benzylamine proved to be strongly stabilizing relative to unmetalated benzylamine and modestly stabilizing relative to an extra A•T base pair. The stabilization was largely abolished in the presence of 2-mercaptoethanol, suggesting direct coordination of Pd(II) to a nucleobase of the complementary strand. In all cases, fidelity of Watson-Crick base pairing between the two strands was retained. Hybridization of the cyclopalladated oligonucleotides was characterized by relatively large negative enthalpy and entropy, consistent with stabilizing Pd(II) coordination partially offset by the entropic penalty of imposing conformational constraints on the flexible diethylene glycol linker between the oligonucleotide and the palladacyclic moiety.
已经制备了 5'-末端带有环钯化苄胺部分的短寡核苷酸，以测试通过与导向寡核苷酸缀合赋予钯环抗癌剂序列选择性的可能性。通过在不存在和存在竞争配体（2-巯基乙醇）的情况下进行 UV 和 CD（圆二色性）熔融实验研究了这些寡核苷酸与天然对应物的杂交。与未金属化的苄胺相比，环钯化苄胺具有很强的稳定性，与额外的 A•T 碱基对相比则具有适度的稳定性。在 2-巯基乙醇存在下，稳定性大大降低，表明 Pd(II)直接与互补链的碱基配位。在所有情况下，两条链之间的 Watson-Crick 碱基配对的保真度都得到保留。环钯化寡核苷酸的杂交具有相对较大的负焓和熵，这与 Pd(II)配位的稳定性一致，部分抵消了在寡核苷酸和钯环部分之间的柔性二甘醇连接物上施加构象约束的熵罚。
