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.

有关生物分子溶解度的知识对于氨基酸、肽、蛋白质和药物生产的设计和优化至关重要。产品纯度、溶液中生物分子的过饱和比率以及合适溶剂的选择取决于溶解度。在许多情况下，关于温度、pH值、助溶剂和共溶质的种类和浓度等参数对生物分子溶解度影响的数据不足。因此，溶解度行为建模引起了化学工程科学的研究兴趣。然而，使用热力学模型的纯溶解度预测的结果仍然不能令人满意。这主要是由于生物分子熔化特性的数据错误或不可用造成的。使用传统方法对熔化特性（如熔化温度 TSL、熔化焓 SL 或热容 cpSL）进行实验测定常常会因生物分子在低于 TSL 的温度下分解而失败。应用可用于估计熔化特性的群体贡献方法可能会产生非常高的不确定性，甚至产生不一致的数据。近年来，开发了快速扫描芯片量热法 (FSC) 新方法，以便通过实验确定熔化特性（TSL、hSL、cpSL）。这对于生物分子特别重要，因为这些化合物在熔化之前会分解。与传统方法（< 1K/s）相比，采用非常高的加热速率（< 10Mio.K/s）可以显着减少高温下的分解时间。因此分解发生在更高的温度下。相比之下，熔化仅轻微取决于加热速率。这允许相变和熔化特性的实验测定。在这个拟议项目中，FSC 将得到进一步开发，以确定生物分子（氨基酸、肽、蛋白质）的 TSL、hSL 和 cpSL 的定量数据。由于二肽的溶解度和熔化特性尚未得到很好的研究，因此二肽的化合物类别应成为该项目的重点关注对象。 FSC 确定的熔化特性将被用作热力学模型的输入，以预测固液平衡。这将允许根据温度和 pH 值预测生物分子在溶剂和溶剂混合物中的溶解度。为了实现这一目标，平衡热力学和实验量热学这两个互补的研究领域必须结合起来。这些领域属于申请该项目的Christoph Held和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