Toward high-throughput drug screening on a chip-based parallel affinity separation platform.

Area of Science:

• Biochemistry
• Analytical Chemistry
• Drug Discovery

Background:

• High-throughput screening (HTS) is crucial for identifying drug candidates from compound libraries.
• Weakly binding ligands are challenging to detect using traditional HTS methods.
• Albumin is a well-established model protein for studying drug-protein interactions.

Purpose of the Study:

• To demonstrate parallel zonal weak affinity chromatography in microcolumns on a chip as a viable HTS format.
• To evaluate the method's capability for screening weakly binding ligands.
• To assess the potential of this technology for accelerating drug discovery.

Main Methods:

• Immobilization of bovine serum albumin (BSA) onto microparticulate diolsilica particles.
• Packing of BSA-modified particles into a 24-channel microcolumn cartridge.
• Application of parallel zonal weak affinity chromatography for ligand screening.
• Analysis of chromatograms to determine ligand-protein affinity.

Main Results:

• The developed method successfully screened for weakly binding ligands.
• Affinity information was obtained for ligands in the millimolar range.
• The system demonstrated the capacity to screen thousands of substances daily.
• Albumin served as an effective model system for validating the technique.

Conclusions:

• Parallel zonal weak affinity chromatography on a chip is a promising HTS technology.
• This method enables efficient screening of weakly binding compounds.
• The technology has the potential to significantly advance drug discovery research by enabling rapid screening of large compound libraries.