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Molecular insights into the transport and toxicity of 6-PPD: Interactions with human serum albumin and alpha-glucosidase 6-PPD转运和毒性的分子洞察:与人血清白蛋白和α -葡萄糖苷酶的相互作用
IF 2.2 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-22 DOI: 10.1016/j.bpc.2025.107529
Jing Zhang, Qiang Ma, Honghui Wang, Bin Chen, Yan Li, Yingmin Liao
The rubber antioxidant, N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6-PPD), as an emerging pollutant, is receiving more and more attention recently. This study investigated the intermolecular interactions of 6-PPD with two key biological macromolecules, human serum albumin (HSA) and alpha-glucosidase (AG), to understand the transport and toxic effects of 6-PPD. Using multiple spectroscopic methods and molecular docking technology, the results demonstrated that 6-PPD could bind to both HSA and AG, thereby inducing fluorescence quenching and conformational changes in both proteins. The binding constants were determined to be (5.93 ± 0.20) × 105 and (3.17 ± 0.15) × 104 L mol−1 respectively for HSA-6-PPD and AG-6-PPD systems at 298 K, revealing strong binding affinities. Molecular docking identified specific binding sites and non-covalent interactions of the two systems. MD and Energy decomposition analysis revealed the dynamics conformational changes of the complexes and identified van der Waals and electrostatic interactions as primary binding drivers for both systems, while polar solvation energy impeded complex formation. TYR161, ILE142, and TYR138 dominated HSA-6-PPD stabilization, whereas AG-6-PPD was driven by hydrophobic interactions with TRP1369 and VAL1373, with ARG1377 incurring substantial desolvation penalties. Synchronous fluorescence and circular dichroism spectroscopy indicated that 6-PPD binding did not disrupt the microenvironment of Tyr and Trp residues in HSA and AG, while induced structural alterations in HSA and AG that could affect their physiological function. In-vitro tests showed that 6-PPD inhibited AG activity in a dose-dependent manner, with an IC50 of 8.22 ± 0.44 μmol L−1. ADMET and PASS online tools was used to predict physicochemical properties and multiorgan toxicity. This work provided insights into the transport and molecular toxicity of 6-PPD, highlighting the adverse biological effects associated with this common rubber additive.
橡胶抗氧化剂N-(1,3-二甲基丁基)-N′-苯基-对苯二胺(6-PPD)作为一种新兴的污染物,近年来受到越来越多的关注。本研究探讨了6-PPD与人血清白蛋白(HSA)和α -葡萄糖苷酶(AG)这两个关键生物大分子的分子间相互作用,以了解6-PPD的转运和毒性作用。利用多种光谱方法和分子对接技术,结果表明6-PPD可以同时与HSA和AG结合,从而引起两种蛋白的荧光猝灭和构象变化。在298 K下,HSA-6-PPD和AG-6-PPD的结合常数分别为(5.93±0.20)× 105和(3.17±0.15)× 104 L mol - 1,具有较强的结合亲和力。分子对接确定了两个体系的特异性结合位点和非共价相互作用。MD和能量分解分析揭示了配合物的动态构象变化,并确定范德华和静电相互作用是两种体系的主要结合驱动因素,而极性溶剂化能阻碍配合物的形成。TYR161、ILE142和TYR138主导了HSA-6-PPD的稳定,而AG-6-PPD是由与TRP1369和VAL1373的疏水相互作用驱动的,而ARG1377会产生大量的溶解效应。同步荧光和圆二色光谱显示,6-PPD结合不会破坏HSA和AG中Tyr和Trp残基的微环境,但会引起HSA和AG的结构改变,从而影响其生理功能。体外实验表明,6-PPD对AG活性的抑制呈剂量依赖性,IC50为8.22±0.44 μmol L−1。ADMET和PASS在线工具用于预测理化性质和多器官毒性。这项工作提供了对6-PPD的转运和分子毒性的见解,突出了与这种常见橡胶添加剂相关的不利生物效应。
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引用次数: 0
In silico and in vitro characterization of Phytolacca latbenia (Moq.): QSAR, phytochemical, and toxicological insights into antiglycation and antidiabetic potential 在硅和体外鉴定的植物latbenia (Moq.): QSAR,植物化学和毒理学的见解降糖和降糖的潜力
IF 2.2 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-10 DOI: 10.1016/j.bpc.2025.107526
Tooba Khalid , Hafiz Abdul Rafey , Adnan Amin , Muhammad Kamran , Muhammad Kazim Zargaham , Samir Anis Ross , Shah-Iram Niaz
Diabetes and the related comorbidities have been associated with elevated levels of advanced glycation end products (AGEs). The biochemical process of advanced glycation, is believed to be playing a pivotal role in the development of complications. Since there exists a great deal of promise for natural products offering antidiabetic potential, we studied advanced glycation inhibition and anti-diabetic profile of Phytolacca latbenia (Moq). on fractions and the sorted compounds based on the QSAR and molecular docking analysis. The top two bioactive compounds; Kaempferol and Esculentoside G, were further evaluated for the MD simulation studies at 150 ns run, compared with the standard. Among the tested compounds, Kaempferol presented significant binding energies in MM-GBSA (−48.63 Kcal/mol) and MD simulation studies (73 %) with transcriptional regulator 4F5S. Molecular docking studies revealed that kaempferol formed three hydrogen bonds with Val342, Ser343 and Ser453, along with Pi-Pi stacking and Pi-cation interactions with Trp213 and Arg217 residues of the 4F5S protein. Kaempferol also displayed significant α-glucosidase inhibition (IC50 0.042 ± 2.31 μg/ml) compared to the acarbose (IC50 0.036 ± 0.31 μg/ml). Almost all of the selected compounds demonstrated adherence to the safety requirements established by ADMET investigation. Liquid–liquid partitioning of the crude methanolic extract with solvents of increasing polarity yielded five solvent fractions;the ethyl acetate fraction (ETOA) obtained by liquid–liquid partitioning of the crude extract with ethyl acetate and water proclaimed substantial results in both the non-oxidative (61 %) and oxidative (58 %) antiglycation assays for thiol group estimation. The ethylacetae fraction (ETOA) demonstrated comparatively strong antioxidant activity, with an IC₅₀ value of 13.25 ± 0.69 μg/ml as determined by the DPPH assay. In α-glucosidase assay, Aqueous fraction demonstrated a considerable inhibition with IC50 value of 0.108 ± 0.32 μg /ml compared to the standard (IC50 0.083 ± 0.43 μg/ml). The safety assessment revealed a slight decline in HeLa cell viability, dropping from 82 % at a 2.5 % concentration to 69 % at a 10 % concentration over 24 h, relative to the control.Therefore, Phytolacca latbenia (Moq). and its phytocompounds tested inhibit α-glucosidase and Advanced glycation end product-the process that underlie diabetic complications and may therefore holds great promise as therapeutic agent, with no toxicity concern,against diabetes and related comorbidities.
糖尿病及相关合并症与晚期糖基化终产物(AGEs)水平升高有关。晚期糖基化的生化过程被认为在并发症的发生中起着关键作用。由于天然产物具有很大的抗糖尿病潜力,我们研究了植物的晚期糖基化抑制和抗糖尿病特征。基于QSAR和分子对接分析的馏分和分选化合物。前两种生物活性化合物;山奈酚和Esculentoside G在运行150 ns时与标准对照,进一步评估MD模拟研究。在所测试的化合物中,山奈酚在MM-GBSA中表现出显著的结合能(- 48.63 Kcal/mol),与转录调节剂4F5S的MD模拟研究(73%)。分子对接研究表明山母酚与4F5S蛋白的Trp213和Arg217残基形成了Pi-Pi堆叠和pi -阳离子相互作用,并与Val342、Ser343和Ser453形成了3个氢键。山奈酚对α-葡萄糖苷酶的抑制作用(IC50为0.042±2.31 μg/ml)显著高于阿卡波糖(IC50为0.036±0.31 μg/ml)。几乎所有选定的化合物都符合ADMET调查确定的安全要求。用极性递增的溶剂对粗甲醇提取物进行液液分配,得到5个溶剂馏分;用乙酸乙酯和水对粗提取物进行液-液分配得到的乙酸乙酯部分(ETOA)在非氧化(61%)和氧化(58%)抗糖基化试验中对硫醇基团的估计都有实质性的结果。乙酯组分(ETOA)显示出较强的抗氧化活性,通过DPPH测定,IC₅₀值为13.25±0.69 μg/ml。α-葡萄糖苷酶实验中,水溶液组分的IC50值为0.108±0.32 μg/ml,而标准品的IC50值为0.083±0.43 μg/ml。安全性评估显示,与对照组相比,在24小时内,HeLa细胞存活率从2.5%浓度的82%下降到10%浓度的69%。因此,Phytolacca latbenia (Moq)。经测试,其植物化合物可抑制α-葡萄糖苷酶和晚期糖基化终产物——这一过程是糖尿病并发症的基础,因此作为治疗糖尿病及相关合并症的无毒性药物具有很大的前景。
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引用次数: 0
Sustainable synthesis and functional profiling of Ipomoea hederifolia-derived terpenoids-assisted silver nanoparticles: Mechanistic insights into anticancer, antioxidant, antibiofilm, and anti-quorum sensing activities Ipomoea hederifolia衍生萜类辅助银纳米颗粒的可持续合成和功能分析:抗癌、抗氧化、抗生物膜和抗群体感应活性的机制见解
IF 2.2 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-04 DOI: 10.1016/j.bpc.2025.107524
Khushboo Makwana , Reem Binsuwaidan , Mohd Adnan , Nawaf Alshammari , Mitesh Patel
Silver nanoparticles (AgNPs) synthesized through green chemistry approaches offer a sustainable alternative to conventional methods, with potential applications in various biological fields. In this study, we report the synthesis of AgNPs using terpenoids derived from Ipomoea hederifolia L. (Convolvulaceae). The AgNPs (AgNPs-T) were characterized using UV–Vis spectroscopy, which revealed a surface plasmon resonance (SPR) peak at 452 nm, confirming successful synthesis. Fourier-transform infrared spectroscopy (FTIR) analysis identified functional groups such as hydroxyl and carbonyl that facilitated the reduction of silver ions and acted as stabilizing agents. Transmission electron microscopy (TEM) showed that the AgNPs-T were spherical in shape, with sizes ranging from 4 to 20 nm, and were well-dispersed due to the presence of capping agents from the plant extract. The biological activities of AgNPs-T were evaluated, showcasing potent antibacterial activity against several human pathogenic bacteria. Additionally, AgNPs-T exhibited significant antibiofilm and anti-quorum sensing activities, disrupting biofilm formation and inhibiting bacterial communication. The nanoparticles also demonstrated strong antioxidant properties by scavenging DPPH radicals in a dose-dependent manner. Moreover, cytotoxicity studies using the MTT assay revealed that AgNPs-T exerted dose-dependent anticancer effects against breast cancer (MCF-7) cells. These findings suggest that Ipomoea hederifolia-derived AgNPs possess multifunctional biological activities, making them promising candidates for applications in antimicrobial, antioxidant, and anticancer therapies.
通过绿色化学方法合成银纳米粒子(AgNPs)是一种可持续的替代传统方法的方法,在各种生物领域具有潜在的应用前景。在本研究中,我们报道了利用从旋花科植物中提取的萜类化合物合成AgNPs的方法。利用紫外可见光谱对合成的AgNPs (AgNPs- t)进行了表征,发现在452nm处存在表面等离子体共振峰(SPR),证实了合成成功。傅里叶变换红外光谱(FTIR)分析发现,羟基和羰基等官能团有助于银离子的还原,并起到稳定剂的作用。透射电子显微镜(TEM)显示,AgNPs-T呈球形,大小在4 ~ 20 nm之间,由于植物提取物中的盖层剂的存在,AgNPs-T分散良好。对AgNPs-T的生物活性进行了评价,显示出对几种人类致病菌的强抑菌活性。此外,AgNPs-T表现出显著的抗生物膜和反群体感应活性,破坏生物膜的形成并抑制细菌的交流。纳米颗粒还表现出很强的抗氧化性能,清除DPPH自由基,并呈剂量依赖性。此外,使用MTT试验的细胞毒性研究表明,AgNPs-T对乳腺癌(MCF-7)细胞具有剂量依赖性的抗癌作用。这些发现表明,山茱萸衍生的AgNPs具有多种生物学活性,在抗菌、抗氧化和抗癌治疗方面具有广阔的应用前景。
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引用次数: 0
Mapping the structural changes of LCD-TDP43 during the liquid-liquid phase separation by different spectroscopic platforms 利用不同的光谱平台绘制LCD-TDP43在液-液相分离过程中的结构变化
IF 2.2 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-04 DOI: 10.1016/j.bpc.2025.107525
Milad Amiri , Mohammad Javad Masroor , S. Shirin Shahangian , Reza H. Sajedi , Bijan Ranjbar
A comprehensive understanding of the molecular mechanism underlying the Liquid-Liquid Phase Separation (LLPS) pathway of LCD-TDP43 remains a challenge in the context of its neuropathogenesis. The primary driving force behind the TDP-43 LLPS is the interplay of hydrophobic interactions reinforced by aromatic residues. This study presents a novel, convenient, sensitive, and probe-free approach using excitation-emission matrix (EEM) fluorescence to monitor the microenvironment of aromatic residues and π-π stacking interactions during different stages of the LLPS pathway. Protein local structuring and the alterations in the positions of aromatic residues, individually and collectively, were detected by this life-time 3D fingerprinting. A new intermediate state with a unique α-sheet structure in the liquid droplet state and other transient species up to amyloid fibrils was discovered by CD and FTIR analyses. This structure with an inherent tendency for transition to β-amyloids, has not previously been reported in the context of LCD-TDP43 nor other LLPS-prone proteins. Mapping of hydrophobic clustering during phase separation revealed a continuous increase, accompanied by different surrounding polarities. The formation of distinct protein species within the LLPS pathway (from monomer to fibril), along with the amyloidogenic nature of TDP-43 fibrillation, was also confirmed by AFM analysis and ThT assay. To conclude, the 3D fluorescence method introduced in this study provides an effective and straightforward approach to critical valuable insights into the key π-π interactions in the LLPS-dependent aggregation pathway of LCD-containing IDPs. The novel identification of the α-sheet non-fibrilar intermediates may provide a new perspective for elucidating the aggregation mechanism of these proteins.
全面了解LCD-TDP43液-液相分离(LLPS)途径的分子机制仍然是其神经发病机制的一个挑战。TDP-43 LLPS背后的主要驱动力是芳香残基增强的疏水相互作用的相互作用。本研究提出了一种新颖、方便、灵敏、无探针的方法,利用激发-发射矩阵(EEM)荧光来监测LLPS途径不同阶段芳香族残基和π-π堆积相互作用的微环境。蛋白质局部结构和芳香残基位置的变化,单独和集体,通过这种终身3D指纹检测。通过CD和FTIR分析,发现了液滴态中具有独特α-片结构的新中间态和淀粉样原纤维等瞬态物质。这种结构具有转化为β-淀粉样蛋白的固有倾向,以前在LCD-TDP43或其他llps易感蛋白的背景下尚未报道。在相分离过程中疏水聚类的映射显示出连续的增加,并伴随着不同的周围极性。AFM分析和ThT试验也证实了LLPS途径(从单体到纤维)中不同蛋白质种类的形成,以及TDP-43纤维的淀粉样变性。总之,本研究中引入的3D荧光方法提供了一种有效而直接的方法,可以深入了解含有lcd的IDPs的llps依赖性聚集途径中关键的π-π相互作用。α-片非原纤维中间体的新鉴定可能为阐明这些蛋白的聚集机制提供新的视角。
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引用次数: 0
Exploring impact of cold atmospheric plasma directed self-assembly of glycated bovine serum albumin 探讨低温大气等离子体诱导糖化牛血清白蛋白自组装的影响
IF 2.2 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-08-22 DOI: 10.1016/j.bpc.2025.107516
Ashim Jyoti Bharati , Daphishisha Phawa , Priojeet Daimary , Monalisa Patra , Kamatchi Sankaranarayanan
Bovine Serum Albumin (BSA) is a globular, water-soluble protein widely used as a model system due to its stability, binding capacity, and structural similarity to human serum albumin (HSA). Cold atmospheric plasma (CAP) has emerged as a versatile tool for biomolecule modification, sterilization, food preservation, and wound healing. This study explores the effects of CAP on glycated BSA, focusing on structural and self-assembly processes. SEM analysis reveals that CAP induces distinct protein self-assemblies depending on treatment duration. Thioflavin assays show increased fluorescence intensity in CAP-treated glycated BSA compared to native and glycated BSA, indicating an enhancement in β-sheet content and self-assembly. These findings offer valuable insights into CAP's role in modulating protein structures, with implications for biomaterials, disease mechanisms, and protein engineering.
牛血清白蛋白(Bovine Serum Albumin, BSA)是一种球状水溶性蛋白,由于其稳定性、结合能力和结构与人血清白蛋白(human Serum Albumin, HSA)相似,被广泛用作模型系统。冷大气等离子体(CAP)已成为生物分子修饰,灭菌,食品保存和伤口愈合的多功能工具。本研究探讨了CAP对糖基化BSA的影响,重点是结构和自组装过程。扫描电镜分析显示,CAP诱导不同的蛋白质自组装取决于处理时间。硫黄素实验显示,与天然和糖化的牛血清白蛋白相比,cap处理的糖化牛血清白蛋白荧光强度增加,表明β-片含量和自组装增强。这些发现为CAP在调节蛋白质结构中的作用提供了有价值的见解,对生物材料、疾病机制和蛋白质工程具有重要意义。
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引用次数: 0
Corrigendum to “Effect of disialoganglioside GD3 on the subgel, gel and fluid phases of cationic DODAB vesicles” [biophysical chemistry 326 (2025) 107503] “双胞脂苷GD3对阳离子DODAB囊泡的亚凝胶、凝胶和流体相的影响”[生物物理化学326(2025)107503]的更正。
IF 2.2 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-08-21 DOI: 10.1016/j.bpc.2025.107513
Julia B. Ejarque , Anna C.F. Couto , Thábata Matos , Evandro L. Duarte , M. Teresa Lamy , Julio H.K. Rozenfeld
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引用次数: 0
Unraveling the molecular interaction of Larotrectinib with calf thymus DNA: A comprehensive study using multi-spectroscopic, thermodynamic, and computational techniques 揭示larorectinib与小牛胸腺DNA的分子相互作用:一项使用多光谱、热力学和计算技术的综合研究
IF 2.2 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-08-12 DOI: 10.1016/j.bpc.2025.107512
Manal A. Alossaimi , Taibah Aldakhil , Heba Elmansi , Fathalla Belal , Galal Magdy
The study of the interaction between small molecules and biological macromolecules is a critical area of research with significant implications across various scientific fields. Larotrectinib, a tropomyosin kinase inhibitor, is used to treat patients with solid tumors harboring neurotrophic tyrosine receptor kinase (NTRK) gene fusions. In this investigation, the interaction between larotrectinib and calf thymus DNA (ctDNA) was thoroughly examined using a combination of techniques, including UV–Vis spectrophotometry, spectrofluorimetry, viscosity measurements, ionic strength variation, thermodynamic analysis, molecular dynamics simulations, and docking studies. The results demonstrated a strong binding interaction between larotrectinib and ctDNA, with the drug primarily binding to the minor groove of ctDNA. This binding mode was established through competitive binding assays using ethidium bromide and rhodamine B, as well as UV–Vis spectroscopy and viscosity analysis. The binding constant (Kb) at 298 K, determined using the Benesi-Hildebrand equation, was found to be 4.4 × 105 M−1, pointing out a high binding affinity between larotrectinib and ctDNA. Thermodynamic analysis revealed that the interaction is driven mainly by hydrophobic forces and hydrogen bonding, as evidenced by the calculated enthalpy (ΔH0) and entropy (ΔS0) changes. Molecular docking studies further supported these findings, showing that larotrectinib binds preferentially to the AT-rich regions of the B-DNA minor groove. This was validated by molecular dynamics studies, which provided additional confirmation of the binding mechanism. Overall, these findings provide valuable understanding into the molecular interactions and pharmacological mechanisms of larotrectinib, contributing to a deeper insight of its role as a potent anticancer agent.
小分子与生物大分子之间相互作用的研究是一个重要的研究领域,在各个科学领域都具有重要的意义。larorectinib是一种原肌球蛋白激酶抑制剂,用于治疗含有神经营养酪氨酸受体激酶(NTRK)基因融合的实体瘤患者。在这项研究中,larorectinib和小牛胸腺DNA (ctDNA)之间的相互作用进行了全面的研究,包括紫外可见分光光度法、荧光光谱法、粘度测量、离子强度变化、热力学分析、分子动力学模拟和对接研究。结果表明larorectinib与ctDNA之间具有很强的结合相互作用,药物主要结合在ctDNA的小凹槽上。这种结合模式是通过溴化乙锭和罗丹明B的竞争结合实验,以及紫外可见光谱和粘度分析建立的。利用Benesi-Hildebrand方程确定larorectinib与ctDNA在298 K时的结合常数(Kb)为4.4 × 105 M−1,表明larorectinib与ctDNA具有较高的结合亲和力。热力学分析表明,相互作用主要由疏水力和氢键驱动,计算焓(ΔH0)和熵(ΔS0)的变化证明了这一点。分子对接研究进一步支持了这些发现,表明larorectinib优先结合B-DNA次要凹槽中富含at的区域。分子动力学研究证实了这一点,进一步证实了其结合机制。总的来说,这些发现为larorectinib的分子相互作用和药理机制提供了有价值的理解,有助于更深入地了解其作为一种有效的抗癌药物的作用。
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引用次数: 0
Internalization of external tau aggregates co-localize with early endocytic markers and lysosomes 外源性tau聚集物的内化与早期内吞标记物和溶酶体共定位
IF 2.2 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-08-08 DOI: 10.1016/j.bpc.2025.107505
Francisco Melo , Nicolás Flores , Igor Navarrete , Leonardo Caballero , Alberto Cornejo
Tau's spread and internalization are related to disease progression in Alzheimer's disease and tauopathies. Tau internalization plays a critical role in the spreading. The cells involved in brain surveillance involved in the clearance of aggregates include parenchymal-border macrophages (microglia), perivascular macrophages, and meningeal and choroid plexus macrophages. However, in events such as strokes, or tau amyloids can breach the blood-brain barrier (BBB). Facilitating the dissemination of aggregates. Thus, we evaluated whether the tau aggregates have effect over a semi-permeable layer such as DOPC. Nano-indentation showed that tau monomers of full length and tau 4R (microtubule binding domain) interact differently with DOPC, and the amyloids increase the Fp (critical force) but not disrupt the DOPC. Then, to analyze the effect of aggregates on N2a cells, we incubated tau aggregates for 24 h; resulting in the decrease of axon-like structures compromising the cell integrity. Afterwards, cultured tau aggregates with raw 264.7 cells (mouse macrophages) showed that the 4R microtubule-binding domain co-localize with Rab5 and Lamp1, suggesting a key role to lysosomes in the clearance of tau aggregates.
Tau蛋白的扩散和内化与阿尔茨海默病和Tau病变的疾病进展有关。Tau内化在传播中起着关键作用。参与脑监测和清除聚集物的细胞包括实质边界巨噬细胞(小胶质细胞)、血管周围巨噬细胞、脑膜和脉络膜丛巨噬细胞。然而,在中风等事件中,tau淀粉样蛋白会破坏血脑屏障(BBB)。促进汇总资料的传播。因此,我们评估了tau聚集体是否对半透层(如DOPC)有影响。纳米压痕显示全长tau单体和tau 4R(微管结合域)与DOPC的相互作用不同,淀粉样蛋白增加Fp(临界力),但不破坏DOPC。然后,为了分析聚集物对N2a细胞的影响,我们将tau聚集物孵育24 h;导致轴突样结构减少,损害细胞完整性。随后,用264.7细胞(小鼠巨噬细胞)培养的tau聚集体显示,4R微管结合域与Rab5和Lamp1共定位,这表明溶酶体在tau聚集体的清除中起关键作用。
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引用次数: 0
Effect of disialoganglioside GD3 on the subgel, gel and fluid phases of cationic DODAB vesicles 双胞苷GD3对阳离子DODAB囊泡亚凝胶、凝胶和流体相的影响
IF 2.2 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-08-04 DOI: 10.1016/j.bpc.2025.107503
Julia B. Ejarque , Anna C.F. Couto , Thábata Matos , Evandro L. Duarte , M. Teresa Lamy , Julio H.K. Rozenfeld
GD3 is a disialoganglioside overexpressed in several types of cancer cells. The synthetic cationic lipid DODAB has been successfully employed as a vaccine adjuvant, and would be suitable to enhance GD3 immunogenicity. Here, mixed dispersions of GD3 and DODAB were characterized by Differential Scanning Calorimetry (DSC) and Electron Paramagnetic Resonance (EPR) spectroscopy. GD3 is miscible with DODAB, and decreases the DODAB gel-fluid transition cooperativity. GD3 does not affect the temperature hysteresis between gel-fluid and fluid-gel transitions. GD3 does not affect the formation of a subgel phase in DODAB bilayers cooled below 15 °C. GD3 decreases the acyl chain packing of the DODAB subgel phase, which could explain the broad and shallow exothermic event between 5 °C and 20 °C that appears on thermograms of mixed dispersions. These results might contribute to the development of novel GD3-based cancer immunotherapies, including at the low temperatures involved in cold chain stability.
GD3是一种在几种类型的癌细胞中过表达的双胞脂苷。合成的阳离子脂质DODAB已成功用作疫苗佐剂,可增强GD3的免疫原性。本文采用差示扫描量热法(DSC)和电子顺磁共振(EPR)对GD3和DODAB的混合分散体进行了表征。GD3与DODAB存在混相,降低了DODAB凝胶-流体的迁移协同性。GD3不影响凝胶-流体和流体-凝胶转变之间的温度滞后。GD3不影响冷却至15℃以下的DODAB双分子层中亚凝胶相的形成。GD3减少了DODAB亚凝胶相的酰基链堆积,这可以解释混合分散体在5°C至20°C之间出现的宽而浅的放热事件。这些结果可能有助于开发新的基于gd3的癌症免疫疗法,包括在低温下参与冷链稳定性。
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引用次数: 0
Molecular mechanisms of Lobeline-mediated inhibition of lysozyme amyloidogenesis: A synergistic approach using biophysical and cheminformatics techniques 红叶碱介导的溶菌酶淀粉样蛋白形成抑制的分子机制:使用生物物理和化学信息学技术的协同方法
IF 2.2 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-24 DOI: 10.1016/j.bpc.2025.107502
Vibeizonuo Rupreo , Ria Saha , Jhimli Bhattacharyya , Rajib Kumar Mitra
Numerous pathological conditions, collectively termed amyloidosis, are associated with the aggregation of misfolded proteins under stressed physiochemical conditions. Natural compounds capable of modulating protein aggregation or disassembling preformed fibrils hold promise as potential therapeutic candidates for treating aggregation-related diseases. In this study, we aim to examine the binding interaction and effectiveness of Lobeline (Lob), a piperidine alkaloid, in preventing the formation of acid-denatured Lysozyme (Lyz) amyloid using various spectroscopic, cheminformatics and imaging techniques. Steady-state and time-resolved fluorescence measurements confirm a direct interaction between Lyz and Lob with a binding constant of ∼106 M−1 with a 1:1 binding stoichiometry. The association has been found to be spontaneous and is driven by entropy involving non-electrostatic interactions. Molecular Docking shows that Lob stabilizes Lyz by hydrophobic and hydrophilic interactions. The anti-amyloid properties of Lob in Lyz amyloid fibrils are assessed through a range of in vitro techniques, including turbidity measurement, dynamic light scattering (DLS), Thioflavin T (ThT) fluorescence, Circular Dichroism studies and Field Emission Scanning Electron Microscopy (FESEM) imaging. These studies demonstrate that Lob halts the fibrillation of acid-treated Lyz at the nucleation stage by providing alternative pathways for hydrogen bonding and other weak interactions with key amino acid residues necessary for the formation of oligomers and fibrils.
许多病理条件统称为淀粉样变性,与应激物理化学条件下错误折叠蛋白质的聚集有关。能够调节蛋白质聚集或分解预先形成的原纤维的天然化合物有望成为治疗聚集相关疾病的潜在治疗候选者。在这项研究中,我们旨在利用各种光谱、化学信息学和成像技术研究胡椒碱生物碱Lobeline (Lob)的结合相互作用和有效性,以防止酸变性溶菌酶(Lyz)淀粉样蛋白的形成。稳态和时间分辨荧光测量证实了Lyz和Lob之间的直接相互作用,结合常数为~ 106 M−1,结合化学计量为1:1。这种联系是自发的,是由涉及非静电相互作用的熵驱动的。分子对接表明,Lob通过疏水和亲水性相互作用稳定Lyz。通过一系列体外技术,包括浊度测量、动态光散射(DLS)、硫黄素T (ThT)荧光、圆二色性研究和场发射扫描电子显微镜(FESEM)成像,评估了Lyz淀粉样蛋白原纤维中Lob的抗淀粉样蛋白特性。这些研究表明,Lob通过提供与低聚物和原纤维形成所必需的关键氨基酸残基的氢键和其他弱相互作用的替代途径,在成核阶段阻止了酸处理的Lyz的纤颤。
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Biophysical chemistry
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