Herein, we described the synthesis of two l-phenylalanines α-derivatized with a terminal alkyne moiety whose structures differed by phenyl ring halogen substitution (two o-Cl in 1 vs. one p-Br in 2) and investigated their effect on biological macromolecules and living cells. We explored their interaction with quadruplex DNA (G4 DNA), using tel₂₆ and c-myc as models, and bovine serum albumin (BSA). By CD spectroscopy, we found that 1 caused minor tel26 secondary structure changes, leading also to a slight thermal stabilization of this hybrid antiparallel/parallel G4 structure, while the c-myc parallel topology remained essentially unchanged upon 1 binding. Other CD evidences showed the ability of 1 to bind BSA, while molecular docking studies suggested that the same molecule could be housed into the hydrophobic cavity between sub-domains IIA, IIB, and IIIA of the protein. Furthermore, preliminary aggregation studies, based on concentration-dependent spectroscopic experiments, suggested the ability of 1 to aggregate forming noncovalent polymeric systems in aqueous solution. Differently from 1, the bromine-modified compound was able to bind Cu(II) ion, likely with the formation of a CuL₂ complex, as found by UV spectroscopy. Finally, cell tests excluded any cytotoxic effect of both compounds toward normal cells, but showed slight antiproliferative effects of 2 on PC3 cancerous cells at 24 h, and of 1 on both T98G and MDA-MB-231 cancer cells at 48 h.

中文翻译：

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合成的含炔烃的L-苯丙氨酸衍生物的生物大分子结合和抗癌活性。

本文中，我们描述的合成2升-phenylalaninesα-衍生有其结构由苯环卤素取代不同（两个O-CL在末端炔部分1只与一个p的Br 2）和研究了生物大分子其效果和活细胞。我们使用tel ₂₆和c-myc作为模型以及牛血清白蛋白（BSA）探索了它们与四链体DNA（G4 DNA）的相互作用。通过CD光谱法，我们发现1引起tel26二级结构的微小变化，也导致这种混合反平行/平行G4结构的轻微热稳定，而c-myc平行拓扑在1时基本保持不变捆绑。其他CD证据表明1具有结合BSA的能力，而分子对接研究表明，该分子可以容纳在蛋白质亚结构域IIA，IIB和IIIA之间的疏水腔中。此外，基于浓度依赖性光谱实验的初步聚集研究表明，1具有在水溶液中形成非共价聚合体系的能力。与1不同的是，溴改性的化合物能够结合Cu（II）离子，很可能会形成CuL ₂络合物，这是通过紫外光谱法发现的。最后，细胞试验排除了两种化合物对正常细胞的任何细胞毒性作用，但显示出2的轻微抗增殖作用。对PC3癌细胞在24小时，和1在两个T98G和MDA-MB-231癌细胞在48小时。