Methods for screening compound libraries
OwnerOle Hindsgaul, David C. Schriemerinventors
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Abstract
Disclosed are methods for screening compound libraries using frontal chromatography in combination with mass spectrometry to identify and rank those members of the library that bind to a target receptor. Methods are also disclosed which permit a compound library to be rapidly screened to determine if any member of the library has an affinity for the target receptor as measured by a pre-selected indicator compound.
Claims11
A method for screening a compound library to determine the relative affinity of a plurality of putative ligands to a target receptor or a plurality of target receptors relative to an indicator compound or a plurality of indicator compounds, which method comprises:
- (a) providing a compound library comprising a plurality of putative ligands;
- (b) providing at least one void marker compound;
- (c) providing an indicator compound or a plurality of indicator compounds for each target receptor, each indicator compound having a pre-determined affinity for the target receptor and having a pre-determined break through time on the column in the absence of the compound library relative to a void marker compound;
- (d) applying the compound library to a column comprising a target receptor or a plurality of target receptors, each target receptor selected from the group consisting of proteins, peptides, DNA, DNA fragments, RNA and RNA fragments and optionally bound to a solid phase support, under frontal chromatography conditions to partially equilibrate the column with the compound library;
- (e) applying (i) a mixture comprising the compound library, the void marker compound and the indicator compound or compounds, or (ii) the void marker compound and the indicator compound or compounds, to the column under frontal chromatography conditions to provide an effluent;
- (f) analyzing the effluent to determine a break through time for the indicator compound or compounds;
- and
- (g) determining whether any putative ligands of the compound library have an affinity for a target receptor greater than the indicator compound by comparing the break through time for the indicator compound from step (f) with the predetermined break through time for the indicator compound in the absence of the compound library.
Dependencies are inferred from the claim text.