Rupreo Vibeizonuo, Bhattacharyya Jhimli
Department of Chemistry, National Institute of Technology Nagaland, Chumukedima, Dimapur, Nagaland 797103, India.
J Phys Chem B. 2025 May 15;129(19):4692-4704. doi: 10.1021/acs.jpcb.5c01785. Epub 2025 May 5.
Lobeline (LOB) is a bioactive alkaloid known for its neuroprotective and cognitive-enhancing properties, particularly in mitigating oxidative stress and inflammation associated with neurodegenerative diseases. While LOB has been studied for its pharmacological roles in CNS disorders, substance abuse treatment, and smoking cessation, its molecular interactions with proteins and potential antiamyloid, antiglycation, and antioxidant properties remain largely unexplored. This study addresses this gap by analyzing LOB interactions with ovalbumin (OVA) through advanced biophysical and computational techniques to elucidate its therapeutic potential and inform drug development. Fluorescence spectroscopy confirmed a static quenching mechanism and binding constant () of 10 M with a monopreferential binding site in OVA by LOB. Isothermal titration calorimetry (ITC) indicated an exothermic, entropy-driven interaction, while differential scanning calorimetry (DSC) demonstrated LOB-induced stabilization of OVA. Synchronous fluorescence and red edge excitation shift highlighted LOB's effect on Trp and Tyr residues, while circular dichroism (CD) spectroscopy indicated LOB-induced conformational changes in OVA. Molecular modeling (docking and dynamic simulation) corroborated the experimental findings. Turbidity, thioflavin T (ThT), nile red (NR), 8-anilinonaphthalene-1-sulfonic acid (ANS), CD, and morphological studies confirmed OVA fibril formation, and the aggregation was shown to be inhibited by ligand LOB in vitro. Additionally, d-fructose was used to glycate the OVA protein, creating a model to examine the antiglycation and antioxidant effects of LOB. These aspects are essential for advancing targeted drug design and delivery systems, as they provide vital insights into modern biophysical and biochemical research.
洛贝林（LOB）是一种具有生物活性的生物碱，以其神经保护和认知增强特性而闻名，特别是在减轻与神经退行性疾病相关的氧化应激和炎症方面。虽然已经对LOB在中枢神经系统疾病、药物滥用治疗和戒烟中的药理作用进行了研究，但其与蛋白质的分子相互作用以及潜在的抗淀粉样蛋白、抗糖化和抗氧化特性在很大程度上仍未被探索。本研究通过先进的生物物理和计算技术分析LOB与卵清蛋白（OVA）的相互作用，以填补这一空白，阐明其治疗潜力并为药物开发提供信息。荧光光谱证实了静态猝灭机制以及LOB与OVA中单一优先结合位点的结合常数（）为10 M。等温滴定量热法（ITC）表明是放热的、由熵驱动的相互作用，而差示扫描量热法（DSC）表明LOB诱导OVA稳定。同步荧光和红边激发位移突出了LOB对色氨酸和酪氨酸残基的影响，而圆二色性（CD）光谱表明LOB诱导OVA构象变化。分子建模（对接和动态模拟）证实了实验结果。浊度、硫黄素T（ThT）、尼罗红（NR）、8-苯胺基萘-1-磺酸（ANS）、CD和形态学研究证实了OVA纤维的形成，并且在体外显示配体LOB可抑制聚集。此外，使用d-果糖使OVA蛋白糖基化，创建了一个模型来研究LOB的抗糖化和抗氧化作用。这些方面对于推进靶向药物设计和递送系统至关重要，因为它们为现代生物物理和生化研究提供了重要见解。
