Patent ID: 6694267
Filing Date: 2004-02-17
Classification: B01J,C40B,G01N

Abstract:
A method for identifying a member of a mass-coded molecular library which is a ligand for a first biomolecule but is not a ligand for a second biomolecule, wherein the mass-coded molecular library is of the general formula XYn, n is an integer from 2 to about 6, X is a scaffold and each Y is, independently, a peripheral moiety, wherein each peripheral moiety is derived from member of a peripheral moiety precursor subset, said method comprising the steps of;(a) choosing the peripheral moiety precursor subset comprising: (i) choosing every set of two different peripheral moiety precursors from a peripheral moiety precursor set, said choosing performed in a manner such that for each set of two, if the two peripheral moiety precursors have equal molecular masses, then one of the two is removed, forming a remaining set; (ii) from the remaining set, choosing every set of four peripheral moiety precursors, including for a given set of four, removing one of the four peripheral moiety precursors if a sum of the molecular masses of a first two precursors in the given set of four equals a sum of the molecular masses of a second two precursors in the given set of four peripheral moiety precursors, said choosing forming a remainder set; (iii) from the remainder set, choosing every set of six different peripheral moiety precursors, including for a given set of six, removing one of the six peripheral moiety precursors if a sum of the molecular masses of a first three precursors in the given set of six equals a sum of the molecular masses of a second three precursors in the given set of six, said choosing forming a working selection set; and (iv) from the working selection set of peripheral moiety precursors, choosing said peripheral moiety precursor subset such that said subset comprises a sufficient number of peripheral moiety precursors that there exist at least about 250 distinct combinations of n peripheral moieties derived from said subset, and wherein each of at least about 90% of the combinations of n peripheral moieties has a molecular mass sum that is distinct from the molecular mass sum of all other combinations of n peripheral moieties derived from said subset; (b) contacting the second biomolecule with the mass-coded molecular library, whereby members of the mass-coded molecular library which are ligands for the second biomolecule bind to the second biomolecule to form second biomolecule-ligand complexes and members of the mass-coded library which are not ligands for the second biomolecule remain unbound; (c) separating the second biomolecule-ligand complexes from the unbound members of the mass-coded molecular library; (d) contacting the first biomolecule with the unbound members of the mass-coded molecular library of step (c), whereby members of the mass-coded molecular library which are ligands for the first biomolecule bind to the first biomolecule to form first biomolecule-ligand complexes and members of the mass-coded library which are not ligands for the first biomolecule remain unbound; (e) dissociating the first biomolecule-ligand complexes; and (f) determining the molecular mass of each ligand for the first biomolecule; wherein each molecular mass determined in step (f) corresponds to a set of n peripheral moieties present in a ligand for the first biomolecule which is not a ligand for the second biomolecule, thereby identifying a member of the mass-coded molecular library which is a ligand for the first biomolecule but is not a ligand for the second biomolecule.