TA仪器+等温滴定微量热仪+ NANO ITC

Interactions between water and component materials take place in all steps of dosage from manufacture. These interactions can affect the mechanical, physical and chemical properties and consequently also the behaviour of the material of interest.

Solvated systems can be studied by techniques such as moisture sorption, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and isothermal calorimetry. Although in theory any one of these techniques can provide adequate data on the energy changes associated with solvation or desolvation, in practice isothermal microcalorimetry often provides superior data on pseudo-polymorphs, especially when only small (milligram) samples are available, or when unexpected results are obtained from other thermal techniques. For example, TGA was unable to detect formation of a drug hydrate in the presence of lactose monohydrate since there was no net change in mass associated with exchange of water between the drug substance and the lactose excipient.

The development of monoclonal antibody (Mab) based drugs has undergone considerable growth since the release of the first Mab in the mid-eighties. Intuitive biophysical tools that examine and quantify interactions and conformational dynamics are important in demonstrating and understanding local and global conformational changes. The structure of antibodies as well as other macromolecules is related to its function and efficacy therefore control over these parameters is essential. The association of antigens to antibodies or of antibodies to delivery assemblies such as liposomes or gold nanoparticles can be addressed by isothermal titration calorimetry (ITC) while the folding of antibodies can be assayed using differential scanning calorimetry (DSC). Both techniques offer the advantage of using native solutions and both instruments are offered by TA Instruments.

Proteomics research is uncovering a vast array of new proteins, including enzymes. It is now clear that the old assumption that one gene encodes one protein in incorrect. One gene can encode for several proteins, and many proteins have multiple functions: which function is displayed is controlled by the protein’s molecular environment. The structure and function of a protein are controlled by interactions with macromolecules such as other proteins, nucleic acids and lipids. Studying a protein in isolation (for example, obtaining the crystal or NMR structure of a purified protein) is critical to establishing a structural basis for the protein’s function(s). However, true functional characterization of the protein generally requires manipulation of multi-component systems under stringently-controlled conditions, and evaluating the roles of the physical characteristics of the protein. Proteomics has highlighted the need for a technique that can quantify the interactions between molecules under physiologically-relevant conditions.

Although membrane proteins are very difficult to work with, ultra-sensitive calorimetry can overcome the limitations of many other physical characterization techniques to provide insights into the factors driving membrane protein/lipid assembly and controlling the stability of the complexes.

2019年底在武汉爆发的新冠肺炎(2019 novel coronavirus disease, COVID-19)造成国内外乃至全球的大冲击，无论是医药、经济、贸易及各产业体系均受到巨大考验。藉由全球科学家们日以继夜的努力研究，发现新冠肺炎可能的致病基理；其中较为关键的是新冠病毒感染主要是藉由新冠病毒上的S蛋白(spike protein)，专一性的识别攻击人类细胞受体ACE2 (angiotensin converting enzyme 2)进而引起后续的反应。相较于同是冠状病毒的SARS，COVID-19识别人类细胞受体的专一性更强高出20倍1-3。鉴于新冠肺炎启发，本文将回顾利用等温滴定量热法(isothermal titration calorimetry, ITC)及差式扫描量热法(differential scanning calorimetry, DSC)研究病毒相关的技术文献。期望能对抗病毒药物开发、疫苗、检验试剂及基础研究等领域，提供有用的信息。