原子力显微镜在生物分子间相互作用力的研究

近年来原子力显微镜在测量生物分子间的相互作用力方面取得显著的进步。本文综述原子力显微镜原理以及在生物分子间相互作用方面的研究,为人们理解分子的识别进程,提供一个新的研究方法。     

生物标志化合物立体异构重排的微观物理解释

应用微观粒子波动和分子轨道理论,解释生物标志化合物在沉积体系中自身独有的“电子离域-外质子磁旋反应”的重排机理。首先阐明生物标志化合物立体异构重排的理论依据;然后分别探讨了萜、甾烷类立体异构重排和成熟度对应关系;极性、非极性生物标志化合物异构体重排和油气运移对应关系。     

Discovery of SARS-CoV-2 3CLPro Peptidomimetic Inhibitors through the Catalytic Dyad Histidine-Specific Protein–Ligand Interactions

As the etiological agent for the coronavirus disease 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenges the ongoing efforts of vaccine development and drug design. Due to the accumulating cases of breakthrough infections, there are urgent needs for broad-spectrum antiviral medicines. Here, we designed and examined five new tetrapeptidomimetic anti-SARS-CoV-2 inhibitors targeting the 3C-Like protease (3CL^Pro), which is highly conserved among coronaviruses and essential for viral replications. We significantly improved the efficacy of a ketoamide lead compound based on high-resolution co-crystal structures, all-atom simulations, and binding energy calculations. The inhibitors successfully engaged the catalytic dyad histidine residue (H41) of 3CLPro as designed, and they exhibited nanomolar inhibitory capacity as well as mitigated the viral loads of SARS-CoV-2 in cellular assays. As a widely applicable design principle, our results revealed that the potencies of 3CL^Pro-specific drug candidates were determined by the interplay between 3CL^Pro H41 residue and the peptidomimetic inhibitors.     

抗血管生成药物的研究进展与临床应用

血管生成(angiogenesis)在恶性肿瘤和视网膜病变等疾病过程中发挥着重要作用.随着血管新生的调节机制逐渐被揭示,抗血管生成药物的研发也取得新的突破,目前成功获批上市的抗血管生成靶向药物已达十余种,主要包括小分子多靶点血管靶向药物、大分子单靶点血管靶向药物、内源性泛靶点血管靶向药物3类.本文对抗血管生成策略的理论...     

气相色谱法测定乙烯中微量乙炔的方法改进

将国标GB/T3395-93测定乙烯中微量乙炔的方法进行了改进,采用大口径碳分子筛石英毛细管柱代替了原方法中的填充柱,对色谱操作条件进行了优化,该法具有分析速度快、重复性好、准确度高的特点,适用于乙烯产品及中控的分析,有较大的实用价值。     

Searching proper oligothiophene segment as centre donor moiety for isoindigo-based small molecular photovoltaic materials

Systematic studies on a family of photovoltaic molecules are important for fundamentally understanding the basic principles and the key structural factors that govern their photovoltaic performance. In this work, a series of D²-A-D¹-A-D² type small molecules with isoindigo as acceptor (A), oligothiophene as donor (D¹), and 5-hexyl thiophene as D² were designed, synthesized and studied. The number of thiophene unit in oligothiophene segment is systematically varied from 0 to 4. It has been found this structural parameter have significant influence on their phase transition behaviours, light absorption properties, frontier orbital energy levels, molecular packing structures in both neat and blending films with [6,6]-phenyl-C₆₁-butyric acid methyl ester (PC₆₁BM), charge mobility, phase separation morphology, and as well as photovoltaic performances. The compounds bearing odd number of thiophene unit displayed much better photovoltaic performance than those having even number, while the best performance was given by that having terthiophene as D¹ unit.     

非核苷类抗乙肝病毒小分子抑制剂的研究进展

慢性乙型肝炎病毒(HBV)感染是许多肝疾病,如肝炎、肝硬化和肝癌的病因,至今仍是影响人类健康的全球性问题。当前临床用药主要包括免疫调节剂和能抑制逆转录酶活性的核苷类似物,但免疫调节剂的副作用和核苷类似物的耐受性使得慢性乙型肝炎的临床治疗仍然面临着巨大的挑战,而非核苷类抗HBV药物的研究为这一现状的改变提供了很大机会。综述了近年来报道的非核苷类抗HBV小分子抑制剂,重点对其化学结构、抗HBV活性和构效关系进行了总结。     

DNA molecule stretching through thermo-electrophoresis and thermal convection in a heated converging-diverging microchannel

A novel DNA molecule stretching technique is developed and tested herein. Through a heated converging-diverging microchannel, thermal convection and thermophoresis induced by regional heating are shown to significantly elongate single DNA molecules; they are visualized via a confocal laser scanning microscopy. In addition, electrophoretic stretching is also implemented to examine the hybrid effect on the conformation and dynamics of single DNA molecules. The physical properties of the DNA molecules are secured via experimental measurements.     

低能电子冲击下,环己烷的离解

使用自行设计组装调试的离解谱仪,研究了环己烷(C_6H_(12))蒸汽样品在低能电子冲击下的离解产物。实验表明出现的主要产物是质量数为56,68及84的离子。