Experimental Determination of Melting Properties of Biological Compounds for Better Solubility Predictions

生物化合物熔融特性的实验测定，以更好地预测溶解度

• 批准号: 327337994
• 负责人: Dr. Yeong Zen Chua
• 金额: --
• 依托单位: Lehrstuhl für Thermodynamik (TH)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/327337994?language=en
• 关键词: Experimental; Determination; Melting; Properties; Biological

Knowledge about solubility of biomolecules is crucial for the designand optimization of production of amino acids, peptides, proteins, andpharmaceuticals. Product purity, supersaturation ratios ofbiomolecules in solution as well as choice of a suitable solventdepend on solubility. In many cases, data on the influence ofparameters like temperature, pH-value, kind and concentration of cosolventsand co-solutes on biomolecule solubility are insufficient.Modeling solubility behavior has thus attracted research interest inchemical engineering science. However, the results of pure solubilitypredictions using thermodynamic models are still not satisfying. Thisis mainly caused by wrong or not available data of the meltingproperties of the biomolecules. The experimental determination ofmelting properties such as melting temperature TSL, melting enthalpyhSL, or heat capacities cpSL with conventional methods often failscaused by decomposition of the biomolecules at temperatures belowTSL. Application of group-contribution methods that might be used toestimate melting properties might yield to very high uncertainties oreven to non-consistent data. In the last years, the new method FastScanning Chip Calorimetry (FSC) has been developed in order todetermine melting properties (TSL, hSL, cpSL) experimentally. This isof special importance for biomolecules, as these compoundsdecompose before melting. Applying of very high heating rates (< 10Mio. K/s) allows reducing the time for decomposition at hightemperatures dramatically compared to conventional methods (< 1K/s). Decomposition thus takes place at much higher temperatures. Incontrast, melting depends only slightly on heat rate. This allows phasechange and experimental determination of melting properties. In thisproposed project, FSC will be further developed in order to determinequantitatively data for TSL, hSL and cpSL for biomolecules (aminoacids, peptides, proteins). The compound class of dipeptides shall bewithin closer focus of this project as solubility and melting propertiesof dipeptides are not well investigated. The melting properties whichwill be determined by FSC will be used as input into thermodynamicmodels for the prediction of solid-liquid equilibria. Thiswill allowpredicting the solubility of biomolecules in solvents and solventmixtures depending on temperature and pH-value. In order to reach the goal, the complementary research fields equilibriumthermodynamics and experimental calorimetry have to be combined.These fields belong to the research competences of Christoph Heldand Andreas Wurm, who are applying for this project.

关于生物分子的溶解度的知识对于氨基酸，肽，蛋白质和植物学的生产的设计和优化至关重要。溶液中生物分子的产物纯度，过饱和比以及选择合适的溶剂依赖于溶解度。在许多情况下，有关参数的影响，例如温度，pH值，颜料和共溶剂对生物分子溶解度的影响不足。进行研究的溶解度行为吸引了研究兴趣的倾向工程学。但是，使用热力学模型的纯溶解度预测结果仍然不令人满意。这主要是由于生物分子的熔融植物的错误或不可用的数据引起的。熔融特性的实验确定，例如熔化温度TSL，熔融焓或热能CPSL，通常通过在TSL以下的温度下分解生物分子而导致的传统方法。可能使用的小组分配方法的应用可能会导致非常高的不一确定性，从而对非一致的数据产生了很高的不确定性。在过去的几年中，已通过实验性地开发了新方法快速扫描量热法（FSC）（TSL，HSL，CPSL）。对于生物分子而言，这种ISOF特别重要，因为这些化合物在熔化前会构成。与常规方法相比，应用非常高的加热速率（<10mio。K/s）可以大大减少分解时间（<1K/s）。因此，分解发生在更高的温度下。不对比，熔化仅略微取决于热速率。这允许对熔融特性进行浮力和实验确定。在这个规定的项目中，将进一步开发FSC，以确定生物分子（氨基酸，肽，蛋白质）的TSL，HSL和CPSL的量表数据。二肽的化合物类别应更接近该项目，因为二肽的溶解度和熔融性能不太精心研究。通过FSC确定的熔融特性将用作对热力学模型的输入，以预测固液平衡。这将允许预测生物分子在溶剂和溶剂中的溶解度，具体取决于温度和pH值。为了实现目标，必须合并互补的研究领域平衡热力学和实验量热法。这些领域属于正在申请该项目的Christoph Heldreas Andreas Wurm的研究能力。

项目成果

Melting Properties of Peptides and Their Solubility in Water. Part 2: Di- and Tripeptides Based on Glycine, Alanine, Leucine, Proline, and Serine

• DOI: 10.1021/acs.iecr.0c05652
• 发表时间: 2021-02-08
• 期刊: INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
• 影响因子: 4.2
• 作者: Hoang Tam Do;Chua, Yeong Zen;Held, Christoph
• 通讯作者: Held, Christoph