Identification of non-covalent complexes by mass spectrometry
OwnerThomas R. Gadek, Denise Ockeyinventors
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Abstract
Methods for identifying novel drug leads or binding compounds that have an affinity for a target molecule involving screening known drug fragment molecules and derivatives thereof, preferably using mass spectrometry are disclosed.
Claims20
A method for identifying compounds that bind to a target of interest, comprising:
- (a) assembling a first set of target binding ligands that compete for non-covalent binding to a first binding site on the target;
- (b) assembling a second set of target binding ligands that compete for non-covalent binding to a second binding site on the target;
- (c) chemically linking at least one member of the first set and at least one member of the second set to provide a first set of linked ligands;
- and
- (d) screening the set of linked ligands to identify members thereof that bind to the target.
The method of any of the previous claims, wherein the first binding site is the same as the second binding site.
The method of any of the previous claims, wherein the first binding site is not the same as the second binding site.
The method of any of the previous claims, wherein assembling step (b) comprises determining binding of target binding ligands to the target having at least one member of the first set of target binding ligands bound thereto.
The method of any of the previous claims, wherein the target is a target biomolecule.
The method of any of the previous claims, wherein step (c) comprises forming a covalent bond linking the member of the first set and the member of the second set.
The method of any of the previous claims, wherein screening step (d) comprises a biological measurement.
The method of any of the previous claims, wherein a member of the first set and a member of the second set bind to the target in a 1:1 ratio.
The method of any of the previous claims, wherein further comprises assembling a third set of target binding ligands that compete for binding to the first binding site on the target and a fourth set of target binding ligands that compete for binding to the first binding site on the target, where members of each of the third set and the fourth set compete with members of the first set for binding to the first binding site, but members of the third set do not compete with members of the fourth set for binding to the target.
A method of preparing a drug lead compound that binds to a target, comprising covalently linking at least one member of a first set of target binding ligands that compete for non-covalent binding to a first binding site on the target and at least one member a second set of target binding ligands that compete for non-covalent binding to a second binding site on the target set to provide a first set of linked ligands.
Dependencies are inferred from the claim text.