This study delves into the impact of two synthetic non-natural amino acids, 7 and 8, on the structural dynamics of serum albumin and their potential significance in anticancer drug delivery systems. Crucially, the dihydrofuran-containing compound 7 has been identified to bind to the G-quadruplex (G4) DNA sequence 22-mer Pu22, a mimic of the proto-oncogene c-Myc, as ascertained by circular dichroism (CD) and UV spectroscopy. Our docking studies suggest that 7 binds to the G4 structure from the side of the G-quartet in a quasi-parallel manner, engaging in ten intermolecular interactions, including hydrogen bonds, π-lone pair and π-alkyl interactions. Notably, one interaction involves the heterocyclic ring of the compound. Compound 7 emerges as a notable structure modulator, showcasing a significant enhancement in protein α helix formation, as observed in a serum albumin binding CD experiment, and the capability to form supramolecular networks, as evidenced by dynamic light scattering (DLS) and Scanning Electron Microscopy (SEM), with the added benefit of encapsulating the natural anticancer drug curcumin within its self-assemblies. Toxicity assessments on human fibroblast cell lines demonstrate that both compounds are non-toxic, highlighting their biocompatibility and potential for safe biomedical applications. Interestingly, the triazole-based compound 8 induces distinctive structural changes in serum albumins, elucidated through CD and UV spectra using bovine serum albumin (BSA) as a model albumin target.

Keywords: G-quadruplex; MT: Oligonucleotides: Therapies and Applications; Scanning Electron Microscopy; asymmetric synthesis; c-Myc; fluorescence; heterocyclic compounds; molecular docking; non-natural amino acids; oncogene; spectroscopy.

© 2025 The Authors.

这项研究探讨了两种合成非天然氨基酸7和8对血清白蛋白结构动力学的影响及其在抗癌药物递送系统中的潜在意义。关键的是，含二氢呋喃的化合物7已被确认能与G-四链体（G4）DNA序列22-mer Pu22结合，这是原癌基因c-Myc的一个模拟物，这一点通过圆二色谱(CD)和紫外光谱(UV)得到证实。我们的对接研究表明，7以准平行方式从G-四链体的一侧与G4结构结合，并参与了包括氢键、π孤对和π烷基相互作用在内的十个分子间相互作用。值得注意的是，其中一个相互作用涉及到化合物的杂环部分。化合物7展现出了一个显著的结构调节剂特性，在血清白蛋白结合CD实验中观察到蛋白质α螺旋形成的显著增强，并且能够形成超分子网络，这一点通过动态光散射(DLS)和扫描电子显微镜(SEM)得到证实，并且具有将天然抗癌药物姜黄素封装在其自组装体中的能力。在人类成纤维细胞系上的毒性评估表明这两种化合物均无毒，突出了它们的生物相容性及其潜在的安全生物医学应用。有趣的是，基于三唑的化合物8通过使用牛血清白蛋白(BSA)作为模型靶标白蛋白，在CD和UV光谱中引发了血清白蛋白的独特结构变化。

关键词：G-四链体；MT: 寡核苷酸：疗法与应用；扫描电子显微镜；不对称合成；c-Myc；荧光；杂环化合物；分子对接；非天然氨基酸；癌基因；光谱学。