IRBM Science Park S.p.A., Via Pontina km 30.600, 00071, Pomezia, Rome, Italy.
Dipartimento di Scienze e Tecnologie Chimiche, Università di Roma "Tor Vergata", Via della Ricerca Scientifica, 00133, Rome, Italy.
J Pharm Biomed Anal. 2019 Apr 15;167:21-29. doi: 10.1016/j.jpba.2019.01.049. Epub 2019 Jan 31.
A new methodology based on Nuclear Magnetic Resonance (NMR) was developed to determine plasma protein binding (PPB) of drug candidates in drug discovery programs. A strong correlation was found between the attenuation of NMR signals of diverse drugs in the presence of different plasma concentrations and their fraction bound (f) reported in the literature. Based on these results, a protocol for a rapid calculation of f of small molecules was established. The advantage of using plasma instead of purified recombinant proteins and the possibility of pool analysis to increase throughput were also evaluated. This novel methodology proved to be very versatile, cost-effective, fast and suitable for automation. As a plus, it contemporarily provides a quality check and solubility of the compound.
一种基于核磁共振（NMR）的新方法已被开发出来，用于确定药物发现项目中候选药物的血浆蛋白结合率（PPB）。研究发现，不同药物在存在不同血浆浓度的情况下，其 NMR 信号的衰减与文献中报道的其结合分数（f）之间存在很强的相关性。基于这些结果，建立了一种快速计算小分子 f 值的方案。还评估了使用血浆而不是纯化的重组蛋白的优势，以及池分析以提高通量的可能性。这种新方法被证明非常通用、具有成本效益、快速且适合自动化。此外，它还可以同时提供化合物的质量检查和溶解度。
