Abstract

G-quadruplex DNA in recognized as a potential target for anti-cancer drugs. In this work, an anthraquinonecarboxamido derivative of β-cyclodextrin (AQCC) is synthesized as a novel DNA binder that further can deliver an additional molecule at the target, carrying it in the cavity of modified cyclodextrin. The binding of AQCC with ethidium bromide (EtBr), berberine (Ber), duplex calf-thymus DNA (CT-DNA), quadruplexes (G4) viz., kit22, myc22, and telo24 are studied. The compound acts as a host molecule for the encapsulation of DNA binders viz., EtBr, Ber and enhances their fluorescence due to the encapsulation in its AQCC’s cyclodextrin cavity. The binding constant of the host: guest complex of EtBr and Ber with AQCC’s cavity are 6.4 × 10⁵ and 3.3 × 10⁶ mol⁻¹ dm³, respectively. The proximity of the protons of the guest and host molecules is confirmed by two-dimensional rotating-frame Overhauser effect spectroscopy (2D ROESY). The conjugate displays a quenching of fluorescence selectively on the association with CT-DNA and quadruplex kit22 that is contrast to the spectral behavior with quadruplex myc22 and telo24. CT-DNA exhibits dissimilar fluorescence spectra in free- and EtBr-bound forms. In addition, kit22 exhibit dissimilar emission profile when AQCC encapsulates Ber. Therefore, the Ber-loaded complexes and the AQCC molecule bind to different G-quadruplexes with different binding strengths. In addition, the effect of Ber in binding to the target DNAs is pronounces since the Ber molecule has more affinity to bind to quadruplexes than the duplex.

摘要

G-四链体 DNA 被认为是抗癌药物的潜在靶点。在这项工作中，β-环糊精的蒽醌甲酰胺衍生物 (AQCC) 被合成为一种新型 DNA 结合剂，该结合剂可以进一步在靶标处传递一个额外的分子，并将其携带在修饰的环糊精腔中。研究了 AQCC 与溴化乙锭 (EtBr)、小檗碱 (Ber)、双链小牛胸腺 DNA (CT-DNA)、四链体 (G4) 即kit22、myc22和telo24的结合。该化合物充当封装 DNA 结合剂（即 EtBr、Ber）的宿主分子，并由于封装在其 AQCC 的环糊精腔中而增强了它们的荧光。主体的结合常数：EtBr和Ber与AQCC腔的客体复合物为6.4×10 ⁵和 3.3 × 10 ⁶  mol ^-1  dm ³，分别。客体分子和主体分子的质子的接近性通过二维旋转框架 Overhauser 效应光谱 (2D ROESY) 得到证实。偶联物在与 CT-DNA 和四链体试剂盒22的关联上选择性地显示荧光猝灭，这与四链体 myc22和telo24的光谱行为形成对比。CT-DNA 在游离形式和 EtBr 结合形式中表现出不同的荧光光谱。此外，kit22当 AQCC 封装 Ber 时表现出不同的发射曲线。因此，负载 Ber 的复合物和 AQCC 分子以不同的结合强度与不同的 G-四链体结合。此外，由于 Ber 分子与四链体的结合比双链体具有更高的亲和力，因此 Ber 与目标 DNA 结合的作用很明显。