IF 4.354 2区化学 Q1 CHEMISTRY, ORGANIC

Journal of Organic Chemistry

Pub Date : 2026-02-09 DOI: 10.1021/acs.joc.5c03076

Subrata Das, Sujan De, Balaram Mukhopadhyay

The total synthesis of the complex pentasaccharide repeating unit related to the O-polysaccharide from Aeromonas hydrophila Pt679 is reported. Suitably protected derivatives of the rare β-d-QuiNAc and α-d-Fuc3NAc units are synthesized from d-glucosamine hydrochloride and 1,2;5,6-di-O-isopropylidene-α-l-allofuranose, respectively, and used for stereoselective glycosylation. The 1,2-cis rhamnosidic linkage is successfully accomplished using picoloyl-mediated hydrogen bond-assisted aglycon delivery (HAD method). The target pentasaccharide in the form of its 2-aminoethyl glycoside is ready for further conjugation through the terminal amine functionality without hampering the reducing end stereochemistry.

报道了与嗜水气单胞菌Pt679 o -多糖相关的复合五糖重复单元的全合成。以盐酸d-氨基葡萄糖和1,2为原料，合成了稀有的β-d-QuiNAc和α-d-Fuc3NAc的适当保护衍生物；分别为5,6-二- o -异丙基-α-l-己呋喃糖，并用于立体选择性糖基化。利用picoloyl介导的氢键辅助糖苷传递（HAD法）成功地完成了1,2-顺式鼠李糖苷的连接。目标五糖以其2-氨基乙基糖苷的形式准备通过末端胺官能进一步偶联，而不妨碍还原端立体化学。

引用次数: 0

Mechanistic Determinants of Oriented Enzyme Immobilization from Martini Simulations 定向酶固定的机制决定因素从马提尼模拟

IF 6.475 2区化学 Q2 CHEMISTRY, PHYSICAL

The Journal of Physical Chemistry Letters

Pub Date : 2026-02-09 DOI: 10.1021/acs.jpclett.5c03753

Juan Carlos Jiménez-García,Nicoll Zeballos,Fernando López-Gallego,Xabier López,David De Sancho

Although enzyme immobilization is widely used in biotechnology, it still poses challenges as a result of the trade-offs among stability, activity, and surface interactions. Computer simulations offer a promising aid to exploring the effects of different immobilization sites and surface chemistry on both the conformational dynamics and catalytic activity of these biomolecules. Here, we introduce a protocol based on a structure-based version of the Martini coarse-grained simulation model (Go̅Martini) to explore how surface tethering geometry influences the structure and function of immobilized Bacillus stearothermophilus alcohol dehydrogenase (BsADH). We compare traditional His-tag tethering with two engineered histidine cluster variants, analyzing their behavior in both soluble and surface-tethered states. We find that cluster-based immobilization locally restricts flexibility in surface-contacting subunits while preserving the mobility of exposed regions, resulting in an enhanced conformational stability under thermal stress. Functional analyses reveal that the ethanol association rates remain largely unaffected by surface attachment, whereas the dissociation of NADH is significantly slowed, explaining the reduced catalytic efficiency. These trends align with experimental findings and highlight the predictive power of Go̅Martini simulations in capturing key functional trade-offs. Altogether, this work offers mechanistic insight into the rational design of immobilized biocatalysts and outlines a practical framework for in silico exploration of enzyme–surface systems.

尽管酶固定化在生物技术中应用广泛，但由于其稳定性、活性和表面相互作用之间的权衡，它仍然面临挑战。计算机模拟为探索不同固定位点和表面化学对这些生物分子的构象动力学和催化活性的影响提供了有希望的帮助。在这里，我们介绍了一种基于结构的Martini粗粒度模拟模型（Go _ Martini）的方案，以探索表面捆绑几何形状如何影响固定化的嗜热脂肪芽孢杆菌醇脱氢酶（BsADH）的结构和功能。我们比较了传统的his标签捆绑和两种工程组氨酸簇变体，分析了它们在可溶性和表面捆绑状态下的行为。我们发现基于团簇的固定局部限制了表面接触亚基的灵活性，同时保持了暴露区域的流动性，从而增强了热应力下的构象稳定性。功能分析表明，乙醇缔合速率在很大程度上不受表面附着的影响，而NADH的解离则显著减慢，这解释了催化效率降低的原因。这些趋势与实验结果一致，并突出了Go′s Martini模拟在捕获关键功能权衡方面的预测能力。总之，这项工作为固定化生物催化剂的合理设计提供了机械洞察力，并概述了酶表面系统的硅探索的实用框架。

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引用次数: 0

Phase Behavior of Polluted and Clean Urban Winter PM2.5 from Optical Observations and Thermodynamic Equilibrium Modeling 基于光学观测和热力学平衡模型的污染和清洁城市冬季PM2.5相行为

IF 9.028 1区环境科学与生态学 Q1 ENGINEERING, ENVIRONMENTAL

环境科学与技术

Pub Date : 2026-02-09 DOI: 10.1021/acs.est.5c16878

Tien Van Do,Andreas Zuend,Na Rae Choi,Taehyoung Lee,Hyejung Shin,Kwangyul Lee,Jongsung Park,Seokjun Seo,Mijung Song

The phase state of fine particles (PM2.5) critically governs gas–particle partitioning and multiphase chemical reactivity, yet remains poorly constrained under real-world conditions. In this study, optical microscopy, poke-and-flow experiments, and thermodynamic modeling were combined to examine the phase behavior of wintertime urban PM2.5 collected in Ansan, South Korea. Morphological analyses revealed humidity- and composition-dependent transitions, with liquid–liquid and liquid–liquid–solid states frequently observed in individual particles. Polluted, nitrate-rich aerosols predominantly exhibited liquid-like morphology and followed near-equilibrium partitioning of nitrate and ammonium. In contrast, cleaner, organic-rich particles likely exhibited higher viscosity and nonliquid characteristics, which may have led to partial deviation from equilibrium predictions. These results provide direct experimental evidence of phase complexity in ambient PM2.5 and demonstrate that the particle phase state, modulated by relative humidity and composition, plays a critical role in determining thermodynamic behavior and atmospheric reactivity of urban aerosols.

细颗粒（PM2.5）的相态对气粒分配和多相化学反应性起着至关重要的作用，但在现实条件下仍然缺乏约束。在这项研究中，结合光学显微镜、戳流实验和热力学模型，研究了在韩国安山收集的冬季城市PM2.5的相位行为。形态分析揭示了湿度和成分依赖的转变，在单个颗粒中经常观察到液-液和液-液-固状态。受污染的、富含硝酸盐的气溶胶主要表现为液体状形态，并遵循硝酸盐和铵的近平衡分配。相比之下，更清洁、富含有机物的颗粒可能表现出更高的粘度和非液体特性，这可能导致部分偏离平衡预测。这些结果为环境PM2.5的相复杂性提供了直接的实验证据，并表明由相对湿度和成分调节的颗粒相状态在决定城市气溶胶的热力学行为和大气反应性方面起着关键作用。

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引用次数: 0

Anomaly-Detection-Driven Screening of Thermodynamic Stability from Composition Descriptors Alone 异常检测驱动的单组分描述符热力学稳定性筛选

IF 6.475 2区化学 Q2 CHEMISTRY, PHYSICAL

The Journal of Physical Chemistry Letters

Pub Date : 2026-02-09 DOI: 10.1021/acs.jpclett.5c03772

Keisuke Makino, Yudai Yamaguchi, Naoto Tanibata, Hayami Takeda, Ryo Kobayashi, Masayuki Karasuyama, Masanobu Nakayama

Materials informatics tends to rely on existing structural database searches that constrain exploration by omitting unregistered compositions. In this study, an autoencoder-based anomaly detector was developed using composition-only descriptors as input features. The model was trained on thermodynamically stable phases─defined as those on the convex hull with an energy above hull (ΔE_hull) of 0 eV/atom─as well as nearly stable phases with ΔE_hull < 0.01 eV/atom, sourced from the Materials Project inorganic database. The reconstruction error (RMSE) was used as the anomaly score. It was shown that the RMSE increased systematically with apparent thermal destabilization─that is, increasing energy above hull. It was also shown that for 50,000 dummy oxides with an intentionally perturbed charge balance, the RMSE increased in proportion to the magnitude of the total charge imbalance, indicating that departures from charge neutrality could be captured even without explicit charge information. Feature-importance analysis suggested that element pairs (two-element combinations) were the principal factors governing the reconstruction RMSE. Accordingly, for 50,000 charge-compensated virtual oxides, we ordinally encoded the valence-shell type as s = 1, p = 2, d = 3, and f = 4 and defined, for each element pair, a coarse indicator given by the product of the two codes (hereafter, the spdf product). For each pair, we evaluated the correspondence between the median RMSE (taken over all compositions containing that pair) and its spdf product and obtained an approximately monotonic relationship─that is, pairs with smaller spdf products tended to have a lower median RMSE, whereas those with larger spdf products tended to have higher values. By contrast, pairs containing Ta consistently deviated downward from this relationship (i.e., exhibited a lower RMSE), suggesting that not only the spdf product but other descriptor information could also influence the assessment of synthesizability.

材料信息学倾向于依赖现有的结构数据库搜索，通过省略未注册的成分来限制探索。在这项研究中，开发了一个基于自动编码器的异常检测器，使用仅成分描述符作为输入特征。该模型是在热力学稳定相（定义为凸壳上的能量为0 eV/原子（ΔEhull）的相）和接近稳定相（ΔEhull <； 0.01 eV/原子）上进行训练的，这些相来自Materials Project无机数据库。以重建误差（RMSE）作为异常评分。结果表明，随着明显的热失稳（即船体上方能量的增加），RMSE有系统地增加。研究还表明，对于50,000种具有故意干扰电荷平衡的假氧化物，RMSE与总电荷不平衡的大小成比例地增加，这表明即使没有明确的电荷信息，也可以捕获偏离电荷中性的情况。特征重要性分析表明，元素对（两元素组合）是控制重建RMSE的主要因素。因此，对于50,000个电荷补偿的虚拟氧化物，我们通常将价壳类型编码为s = 1, p = 2, d = 3和f = 4，并为每个元素对定义由两个代码的乘积给出的粗指示符（以下称为spdf积）。对于每一对，我们评估了中位数RMSE（包含包含该对的所有组合）与其spdf乘积之间的对应关系，并获得了近似单调关系──即spdf乘积较小的配对往往具有较低的中位数RMSE，而spdf乘积较大的配对往往具有较高的值。相比之下，含有Ta的对始终偏离这一关系（即表现出较低的RMSE），这表明不仅spdf产物，而且其他描述符信息也可能影响可合成性的评估。

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引用次数: 0

Corrigendum to "Redox-mediated synthesis of Kiwi-like hybrid nanoparticles enabling multimode lateral flow immunoassay for detection of cardiac troponin I" [Biosens. Bioelectr. 295 (2026) 118320]. “氧化还原酶介导的猕猴桃样杂交纳米颗粒合成，可用于检测心脏肌钙蛋白I的多模式横向流动免疫分析”的勘误表[Biosens]。生物电学学报，2004,26(3):357 - 357。

IF 10.5 1区生物学 Q1 BIOPHYSICS

Biosensors and Bioelectronics

Pub Date : 2026-02-09 DOI: 10.1016/j.bios.2026.118489

Haodong Wang, Xudong Sun, Fuchao Wu, Zeping Liu, Zhuheng Li, Qian Tong, Zhenxin Wang

引用次数: 0

Optical Properties of Mg2GeO4:Mn4+ Phosphors: From Fine Structures of Vibronic Transitions to the Density of Phonon States Mg2GeO4:Mn4+荧光粉的光学性质：从振动跃迁的精细结构到声子态密度

IF 4.126 3区化学 Q2 CHEMISTRY, PHYSICAL

The Journal of Physical Chemistry C

Pub Date : 2026-02-09 DOI: 10.1021/acs.jpcc.5c07885

Hongyi Zhu,Yitong Wang,Wanggui Ye,Tianlong Ruan,Fei Tang,Jiqiang Ning,Shijie Xu

To address the spectral deficiencies in the red region of commercial white LEDs, developing red-emitting phosphors with reduced dependence on rare-earth elements with limited availability is crucial for spectral compensation. Herein, microstructures and optical characteristics of Mn4+-activated Mg2GeO4 phosphors are presented. While the phosphor exhibits a single orthorhombic phase, its cryogenic micro-Raman and photoluminescence (PL) spectra comprises 19 peaks and three groups of vibronic emissions with wealthy fine structures, respectively. Following the split zero-phonon lines, nine pairs of vibronic lines with an energy separation of 3.5 meV are identified. Furthermore, the overall line shape of the three groups of phonon sidebands can be reproduced by the fully symmetric electron–phonon coupling model, enabling determination of the total density of phonon states. The study sheds light on complicated luminescence fine structures in Mn4+-activated oxide phosphors, offering valuable insights into the design of red-emitting phosphors.

为了解决商用白光led在红色区域的光谱缺陷，开发对可用性有限的稀土元素依赖性较低的红色发光荧光粉是光谱补偿的关键。本文介绍了Mn4+活化的Mg2GeO4荧光粉的微观结构和光学特性。该荧光粉表现为单正交相，其低温微拉曼光谱和光致发光光谱（PL）分别包含19个峰和3组具有丰富精细结构的振动发射。在分裂的零声子线之后，确定了9对能量分离为3.5 meV的振动线。此外，三组声子边带的整体线形可以通过完全对称的电子-声子耦合模型再现，从而可以确定声子态的总密度。该研究揭示了Mn4+活化氧化物荧光粉复杂的发光精细结构，为红发荧光粉的设计提供了有价值的见解。

引用次数: 0

Understanding the Role of Deconjugation of Phase II Metabolites in Wastewater: Implications for Wastewater-Based Epidemiology 了解废水中II期代谢物的脱缀合作用：对废水流行病学的影响

IF 9.028 1区环境科学与生态学 Q1 ENGINEERING, ENVIRONMENTAL

环境科学与技术

Pub Date : 2026-02-09 DOI: 10.1021/acs.est.5c17466

Harry Elliss,Katarina Hricova,Evie Griffiths,Neil Andrew Byrnes,Ben Faill,Eva Hawkins,Kit Proctor,Megan Robertson,John Bagnall,Barbara Kasprzyk-Hordern

Metabolism is a critical bodily function that facilitates the removal of toxic chemical buildup within the body. In wastewater-based epidemiology (WBE), it is crucial to understand the metabolism of biochemical indicators (BCIs) because metabolites are indicative of consumption (e.g., illicit drugs, pharmaceuticals) or unintentional exposure (e.g., pesticides, endocrine disruptors). Phase I metabolites are more widely studied in WBE due to a combination of factors, including, but not limited to, stability and analyte cost. Phase II metabolites are often assumed to deconjugate within the sewer network due to high native concentrations of enzymes. This work deconstructs this assumption and demonstrates how the in-sewer stability of phase II metabolites is dependent on both the parent structure and the conjugate type. In total, 79 BCIs were assessed and compared to urinary metabolism studies via time-variable enzymatic deconjugation using two enzymes, β-glucuronidase and arylsulfatase. The concentrations of free analytes excreted as N-glucuronides, O-glucuronides, and sulfates increased following deconjugation, reinforcing the persistence of these BCIs during transport throughout the sewer network. Conversely, no concentration increase was observed for acylglucuronides, demonstrating complete in-sewer glucuronide cleavage. In-freezer stability of conjugates was also assessed over 6 months, where it was observed that the stability of the parent structure is the driver of stability rather than the conjugates themselves, indicating minimal enzymatic activity upon storage. Overall, this paper presents a framework that can be deployed to gain a more comprehensive understanding of phase II metabolism and improve the accuracy of WBE workflows as well as environmental risk assessment approaches.

新陈代谢是一项重要的身体功能，可以促进体内有毒化学物质的清除。在基于废水的流行病学（WBE）中，了解生化指标（bci）的代谢是至关重要的，因为代谢物是消费（如非法药物、药品）或无意暴露（如农药、内分泌干扰物）的指示物。由于一系列因素，包括但不限于稳定性和分析物成本，I期代谢物在WBE中得到了更广泛的研究。II期代谢物通常被认为在下水道网络中由于高天然浓度的酶而解结。这项工作解构了这一假设，并证明了II期代谢物的下水道稳定性如何依赖于亲本结构和共轭物类型。总共评估了79例bci，并通过两种酶（β-葡萄糖醛酸酶和芳基磺化酶）的时变酶解偶联来比较尿代谢研究。解偶联后，游离分析物以n -葡糖醛酸、o -葡糖醛酸和硫酸盐的形式排出，从而增强了这些bci在整个下水道网络运输过程中的持久性。相反，没有观察到酰基葡萄糖醛酸酯的浓度增加，表明葡萄糖醛酸酯在下水道中完全裂解。偶联物的冷冻稳定性也在6个月内进行了评估，在那里观察到，母体结构的稳定性是稳定性的驱动因素，而不是偶联物本身，这表明在储存时酶活性最低。总的来说，本文提出了一个框架，可以用于更全面地了解II期代谢，提高WBE工作流程的准确性以及环境风险评估方法。

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引用次数: 0

Implications of Off-Peak Commercial Deliveries for Air Quality and Environmental Justice 非高峰商业运输对空气质量和环境正义的影响

IF 9.028 1区环境科学与生态学 Q1 ENGINEERING, ENVIRONMENTAL

环境科学与技术

Pub Date : 2026-02-09 DOI: 10.1021/acs.est.5c07138

Sara Torbatian,Marc Saleh,Laura Minet,Milad Saeedi,Shayamila Mahagammulla Gamage,Daniel Yazgi,Youngseob Kim,Tufayel Chowdhury,James Vaughan,An Wang,Kianoush Mousavi,Matthew J. Roorda,Marianne Hatzopoulou

Urban trucking poses significant health and environmental risks, particularly diesel-fueled trucks. Off-peak delivery (OPD), which refers to the delivery of goods during evening and overnight hours, provides an opportunity to mitigate traffic congestion and improve delivery efficiency. However, the impacts of this delivery schedule on population exposure to air pollution are not clear. This study investigates the spatial distribution of traffic-related air pollutants under two OPD scenarios and assesses their environmental justice implications, in the Greater Toronto and Hamilton Area (GTHA). Using truck movement information from a regional travel demand model and a chemical transport model, we estimated the diurnal changes in air pollutants. The OPD scenarios entail shifting the shares of delivery trips to the evening and overnight periods and account for induced passenger trips during the daytime, resulting from a reduction in truck traffic. One scenario was designed to reflect the industry sectors that would most likely participate in such a scheme and a realistic participation rate, while the other reflects an aggressive shift to overnight periods. While ambient air quality improves during the daytime, despite increased commuter traffic replacing truck movements, air pollutant concentrations worsen at night due to increased emissions under more stable atmospheric conditions. Under both scenarios, the most disadvantaged communities experience the highest variations in air pollution, as they often live close to highways and major truck routes.

城市卡车运输带来了巨大的健康和环境风险，尤其是以柴油为燃料的卡车。非高峰配送（OPD）是指在夜间和夜间配送货物，为缓解交通拥堵和提高配送效率提供了机会。然而，这一交付时间表对人口暴露于空气污染的影响尚不清楚。本研究调查了两种OPD情景下交通相关空气污染物的空间分布，并评估了其对大多伦多和汉密尔顿地区（GTHA）环境正义的影响。利用来自区域旅行需求模型和化学运输模型的卡车运动信息，我们估计了空气污染物的日变化。OPD方案需要将送货行程的份额转移到晚上和夜间，并考虑到卡车交通减少导致的白天乘客的诱导旅行。一种方案旨在反映最有可能参与该计划的行业部门和现实参与率，而另一种方案则反映了向隔夜拆借期的积极转变。虽然白天的环境空气质量有所改善，尽管通勤交通的增加取代了卡车的移动，但由于在更稳定的大气条件下排放增加，空气污染物浓度在夜间恶化。在这两种情况下，最弱势的社区在空气污染方面的变化最大，因为他们通常住在高速公路和主要卡车路线附近。

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引用次数: 0

Aggregation of Huntingtin Exon 1 Proteins at Flat and Curved Membrane Surfaces. 亨廷顿蛋白外显子1蛋白在平面和弯曲膜表面的聚集。

IF 2.9 2区化学 Q3 CHEMISTRY, PHYSICAL

The Journal of Physical Chemistry B

Pub Date : 2026-02-09 DOI: 10.1021/acs.jpcb.5c08562

Mengyan Wang, Carlos Bueno, Peter G Wolynes

Huntingtin exon-1 (HTTex1) aggregation at cellular membranes contributes to the propagation of toxic protein assemblies in Huntington's disease. We explore the thermodynamic and structural mechanisms linking membrane binding, curvature sensing, and nucleation of the aggregates. Here, we use the OpenAWSEM coarse-grained force field code with an effective membrane potential to quantify the folding and surface aggregation behavior of three HTTex1 constructs on both flat lipid bilayers and spherical vesicles. The computed free energy profiles reveal a strong α-helical NT₁₇-mediated affinity (ΔG_bind = -9 kcal/mol) and a curvature-dependent enhancement of this binding, with effective enrichments of protein concentration at the membrane surface of approximately 1000-fold for the NT₁₇ by itself, compared to 18-fold for the polyQ-extended constructs NT₁₇-polyQ and 36-fold for NT₁₇-polyQ-polyP. The free-energy aggregation landscapes demonstrate that membrane proximity also enhances the formation of larger oligomers and promotes early oligomerization through N-terminal anchoring. Analyzing curvature-sensation analyses across vesicle radii shows deeper insertion on highly curved surfaces along with stronger binders, consistent with experimental vesicle-binding assays. Our results establish a mechanistic framework for understanding how membranes can act as two-dimensional platforms that both concentrate HTTex1 and template the formation of aggregation nuclei.

亨廷顿蛋白外显子1 （HTTex1）聚集在细胞膜上有助于亨廷顿病中毒性蛋白组装的繁殖。我们探索了连接膜结合、曲率传感和聚集体成核的热力学和结构机制。在这里，我们使用具有有效膜电位的OpenAWSEM粗粒度力场代码来量化三种HTTex1构建物在扁平脂质双层和球形囊泡上的折叠和表面聚集行为。计算出的自由能谱显示出NT17介导的强α-螺旋亲和力（ΔGbind = -9 kcal/mol）和曲率依赖性的结合增强，NT17本身在膜表面的蛋白质浓度有效富集约为1000倍，而polyq扩展构建体NT17- polyq为18倍，NT17- polyq - polyp为36倍。自由能聚集景观表明，膜邻近也促进了较大低聚物的形成，并通过n端锚定促进了早期低聚。通过对囊泡半径的曲率感觉分析显示，在高度弯曲的表面上插入更深，结合剂更强，与实验囊泡结合分析一致。我们的研究结果建立了一个机制框架，用于理解膜如何作为二维平台，既可以集中HTTex1，又可以模板聚集核的形成。

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引用次数: 0

Physico-Chemical Insights into the Catalytic Inhibition of Plasmodium falciparum Plasmepsin II Activity by Repurposing Fluoroquinolone Drugs. 利用氟喹诺酮类药物催化抑制恶性疟原虫Plasmepsin II活性的理化研究。

IF 2.9 2区化学 Q3 CHEMISTRY, PHYSICAL

The Journal of Physical Chemistry B

Pub Date : 2026-02-09 DOI: 10.1021/acs.jpcb.5c05407

Sadaf Fatima Syed, Pranali Thakur, Mahendra Patil, Sinjan Choudhary

Understanding the molecular basis of enzyme inhibition is crucial for rational drug design, particularly against parasitic targets such as Plasmodium falciparum plasmepsin II (PlmII), an aspartic protease essential for hemoglobin degradation. In this study, we repurposed fluoroquinolone drugs, namely, ofloxacin, levofloxacin, and moxifloxacin, to inhibit the catalytic activity of mature PlmII (mPlmII). Thermodynamic analyses revealed favorable enthalpic and entropic contributions that correlate with the binding strength of each drug to mPlmII. Detailed enzyme kinetics assays, combined with molecular docking studies, demonstrated that moxifloxacin, with an IC₅₀ value of 0.15 ± 0.02 μM, exhibits the most potent inhibition, primarily through hydrogen bonding with the catalytic dyad, Asp34 and Asp214. Quantum mechanics/molecular mechanics (QM/MM) (ONIOM) calculations using B3LYP/6-31G*: UFF further corroborated this binding mode, with donor-acceptor distances ranging from 2.8 to 3.3 Å, consistent with moderate to strong hydrogen bonding. Notably, methylation of the NH group disrupts these critical interactions, altering the ligand's positioning within the active site and resulting in weakened hydrogen bonds and reduced inhibitory efficacy. Overall, our findings reveal that precise hydrogen bonding with Asp34 and Asp214 is essential for the effective inhibition of mPlmII activity, and even minimal structural modifications, such as NH methylation, can impair active site engagement.

了解酶抑制的分子基础对于合理的药物设计至关重要，特别是针对寄生靶点，如恶性疟原虫plasmepsin II (PlmII)，一种对血红蛋白降解至关重要的天冬氨酸蛋白酶。在本研究中，我们重新利用氟喹诺酮类药物，即氧氟沙星、左氧氟沙星和莫西沙星来抑制成熟PlmII （mPlmII）的催化活性。热力学分析显示，有利的焓和熵贡献与每种药物与mPlmII的结合强度相关。详细的酶动力学分析结合分子对接研究表明，莫西沙星的IC50值为0.15±0.02 μM，主要通过与催化二偶体Asp34和Asp214的氢键作用表现出最有效的抑制作用。利用B3LYP/6-31G*: UFF进行的量子力学/分子力学（QM/MM）（ONIOM）计算进一步证实了这种结合模式，供体-受体距离在2.8 ~ 3.3 Å之间，与中强氢键相一致。值得注意的是，NH基团的甲基化破坏了这些关键的相互作用，改变了配体在活性位点内的位置，导致氢键减弱，抑制效果降低。总的来说，我们的研究结果表明，与Asp34和Asp214的精确氢键对于有效抑制mPlmII活性至关重要，即使是最小的结构修饰，如NH甲基化，也会损害活性位点的结合。

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引用次数: 0

化学•材料最新文献