A novel method using nuclear magnetic resonance for plasma protein binding assessment in drug discovery programs.
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 (fb) reported in the literature. Based on these results, a protocol for a rapid calculation of fb 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.
['Gallo|Mariana|M|', 'Matteucci|Sara|S|', 'Alaimo|Nadine|N|', 'Pitti|Erica|E|', 'Orsale|Maria V|MV|', 'Summa|Vincenzo|V|', 'Cicero|Daniel O|DO|', 'Monteagudo|Edith|E|']
D001798:Blood Proteins D055808:Drug Discovery D004353:Drug Evaluation, Preclinical D006801:Humans D066298:In Vitro Techniques D019906:Nuclear Magnetic Resonance, Biomolecular D004364:Pharmaceutical Preparations D011485:Protein Binding D011994:Recombinant Proteins D000075462:Serum Albumin, Human D054852:Small Molecule Libraries
Plasma protein binding Drug discovery NMR Protein-ligand interaction Screening