Drug discovery and development have increasingly been focusing on the identification of unknown ligands from cellular and/or botanical extracts to known biological targets.
As the most abundant protein in blood plasma, human serum albumin (HSA) plays a very important role in drug binding in blood and in transport of bound drugs to the tissues and thus has been used as model protein for diverse biophysical and physiochemical studies.
Since the affinity towards HSA influences the overall distribution, metabolism and efficacy of the ligands, HSA is mostly used as a model biological molecule to investigate the bioactive compounds of botanical extracts.
Based on a few concept-proof studies carried out on ligand fishing of small molecules, Chengdu Institute of Biology (CIB) researchers demonstrated very recently (Nov. 2010) that HSA-MNPs-based ligand fishing can provide an exceptional convenient method to identify small bioactive molecules from botanical extracts.
CIB researchers found that the chemical diversity of secondary metabolites in medicinal plant makes it a huge challenge to isolate the bioactive compounds from herbal extracts, so quick recognition of the bioactive ones is of vital importance for improving the efficiency of isolation.
In this study, a ligand fishing experiment based on human serum albumin functionalized magnetic nano-particles (HSA-MNPs) was performed to probe the bioactive components in a traditional Chinese medicinal plant, Dioscorea panthaica.
The minor compounds fished out by HSA-MNPs were identified by electrospray ionization mass spectrometry (ESI-MS), and then separated from the extract of the whole plant by one or two steps of column chromatography under the guidance of ESI-MS.
Four biologically active compounds, progenin II, progenin III, dioscin and gracillin, were isolated much faster than in the normal lengthy phytochemical procedure. The present study demonstrates that biological macromolecule (protein, enzyme, receptor, et al.) functionalized MNPs may serve as baits to recognize bioactive small molecules in complex herbal extracts.
It is expected that a macromolecule functionalized MNPs-based ligand fishing experiment coupled with ESI-MS may accelerate the process of identification and isolation of bioactive components from medicinal plants, and thus benefit the speed of drug discovery.
The research has receiced grants from National Natural Science Foundation of China(20872137) and National Basic Research Program (973 Program) (2007CB512604) in 2010.
