Mazzitelli Carolyn L, Brodbelt Jennifer S, Kern Jonathan T, Rodriguez Mireya, Kerwin Sean M
Department of Chemistry and Biochemistry, University of Texas at Austin, 1 University Station A5300, 78712-0165, Austin, TX, USA.
Division of Medicinal Chemistry and Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, USA.
J Am Soc Mass Spectrom. 2006 Apr;17(4):593-604. doi: 10.1016/j.jasms.2005.12.011. Epub 2006 Feb 28.
Electrospray ionization mass spectrometry (ESI-MS) and spectroscopic studies in solution were used to evaluate the self-association, G-quadruplex DNA binding, and selectivity of a series of perylene diimides (PDIs) (PIPER, Tel01, Tel11, Tel12, and Tel18) or benzannulated perylene diimide ligands (Tel34 and Tel32). Fluorescence and resonance light scattering spectra of Tel01, Tel12, Tel32, and Tel34 reveal that these analogs undergo self-association in solution. UV-Vis and fluorescence titrations with G-quadruplex, duplex, or single-stranded DNA demonstrate that all the analogs, with the exception of Tel32, bind to G-quadruplex DNA, with those PDIs that are self-associated in solution showing the highest degree of selectivity for binding G-quadruplex DNA. Parallel ESI-MS analysis of the stoichiometries demonstrates the ability of the ligands, with the exception of Tel32, to bind to G-quadruplex DNA. While most ligands show major 1:1 and 2:1 binding stoichiometries as expected in the case of end-stacking, interestingly, three of the most quadruplex-selective ligands show a different behavior. Tel01 forms 3:1 complexes, while Tel12 and Tel32 only form 1:1 complexes. Collisional activation dissociation patterns are compatible with ligand binding to G-quadruplex DNA via stacking on the ends of the terminal G-tetrads. Experiments with duplex and single strand DNA were performed to assess the binding selectivities of the ligands. PIPER, Tel11, and Tel18 demonstrated extensive complexation with duplex DNA, while Tel11 and Tel18 bound to single strand DNA, confirming the lack of selectivity of these two ligands. Our results indicate that Tel01, Tel12, and Tel34 are the most selective for G-quadruplex DNA.
采用电喷雾电离质谱（ESI-MS）和溶液光谱研究方法，对一系列苝二酰亚胺（PDIs）（PIPER、Tel01、Tel11、Tel12和Tel18）或苯并稠合苝二酰亚胺配体（Tel34和Tel32）的自缔合、G-四链体DNA结合及选择性进行了评估。Tel01、Tel12、Tel32和Tel34的荧光光谱及共振光散射光谱表明，这些类似物在溶液中会发生自缔合。用G-四链体、双链或单链DNA进行紫外可见光谱和荧光滴定实验表明，除Tel32外，所有类似物均能与G-四链体DNA结合，其中在溶液中自缔合的那些PDIs对G-四链体DNA的结合选择性最高。对化学计量比进行的平行ESI-MS分析表明，除Tel32外，其他配体均有与G-四链体DNA结合的能力。虽然大多数配体如预期的那样以末端堆积方式呈现主要的1:1和2:1结合化学计量比，但有趣的是，三种对四链体选择性最高的配体表现出不同的行为。Tel01形成3:1的复合物，而Tel12和Tel32仅形成1:1的复合物。碰撞活化解离模式与配体通过堆积在末端G-四联体末端与G-四链体DNA结合的情况相符。进行了双链和单链DNA实验以评估配体的结合选择性。PIPER、Tel11和Tel18与双链DNA有广泛的络合作用，而Tel11和Tel18与单链DNA结合，证实了这两种配体缺乏选择性。我们的结果表明，Tel01、Tel12和Tel34对G-四链体DNA的选择性最高。
