Evaluation of different operation modes of high performance liquid chromatography for the analysis of complex mixtures of neutral oligosaccharides

Chromatographic methods based on different HPLC operation modes, reverse phase (RP), high performance anion exchange chromatography (HPAEC), graphitized carbon chromatography (GCC) and hydrophilic interaction liquid chromatography (HILIC), have been developed and compared for the analysis of complex mixtures of neutral oligosaccharides with functional properties. Whereas GCC gave the best chromatographic separation of isomeric oligosaccharides with the same molecular weight (R(s) values in the range 1.0-4.0 and 2.4-5.6 for tetra- and pentasaccharides, respectively), HILIC provided the best results for mixtures including oligosaccharides of different degrees of polymerization (R(s) values of maltooligosaccharides between 3.4 and 6.2). Validation of the HILIC LC-MS method proved its utility for the analysis of oligosaccharide mixtures with functional properties: relative standard deviations lower than 10%, LOD's and LOQ's in the range 12.7-130.2 ng mL(-1) and 39.3-402.2 ng mL(-1), respectively, and linearity up to 10-20 μg mL(-1). Quantitative data for fructooligosaccharides, gentiooligosaccharides and dextransucrase cellobiose acceptor oligosaccharides were obtained by using this method.     

海绵中提取的异臭椿萜类化合物作用靶标的识别

采取了包括化学结构相似性学习、靶标聚类分析以及反向对接筛选等多种方法在内的综合性策略, 尝试对中国南海海绵中提取得到的异臭椿萜类化合物进行生物学活性和作用靶标的预测. 结果表明: 这类化合物具有治疗心肌缺血和抗肿瘤的潜在生物学活性; 表皮细胞生长因子受体(EGFR), 焦点(局部)粘着斑激酶(FAK), 胰岛素样生长因子1受体 (IGF1-R), c-Src激酶以及血管表皮生长因子受体2 (VEGF-R2)是这类化合物可能的作用靶标. IC₅₀值从0.41 g·m^-3 (0.41 μg·mL^-1)到9.8 g·m^-3 (9.8 μg·mL^-1)不等. 活性数据显示这些海绵提取的海洋天然产物可作为先导化合物, 通过进一步的优化获得新的药物. 同时还讨论了化合物与预测靶标的结合模式, 结果显示四个化合物都与相应的受体有较好的结合.     

Packing nanomechanics of viral genomes

We investigate the osmotic equilibrium between a bulk polyethylene glycol (PEG) solution and DNA tightly packed in a spherical capsid. We base our analysis on the equations of thermodynamic equilibrium in terms of osmotic pressure. The equality between external osmotic pressure of PEG and osmotic pressure of tightly packed DNA gives us the DNA encapsidation curves. In this way we directly connect the wealth of existing osmotic pressure data for DNA in the bulk with the DNA encapsidation curves within small viral capsids. Specific calculations are made for a monovalent salt, Na(+) -DNA and a divalent salt, Mn(2+) -DNA that have quite different DNA encapsidation behaviors. The main conclusion of our work is that bending energy of DNA is of minor importance regarding the encapsidated DNA length, but has a non-negligible influence on the density distribution of DNA within the capsid.     

Temporal Regulation of PET-RAFT Controlled Radical Depolymerization

A photocatalytic RAFT-controlled radical depolymerization method is introduced for precisely conferring temporal control under visible light irradiation. By regulating the deactivation of the depropagating chains and suppressing thermal initiation, an excellent temporal control was enabled, exemplified by several consecutive “on” and “off” cycles. Minimal, if any, depolymerization could be observed during the dark periods while the polymer chain-ends could be efficiently re-activated and continue to depropagate upon re-exposure to light. Notably, favoring deactivation resulted in the gradual unzipping of polymer chains and a stepwise decrease in molecular weight over time. This synthetic approach constitutes a simple methodology to modulate temporal control during the chemical recycling of RAFT-synthesized polymers while offering invaluable mechanistic insights.