Method for producing and screening mass coded combinatorial libraries for drug discovery and target validation

A method for producing a mass-coded set of compounds of the general formula X(Y)n, wherein X is a scaffold, n is from 2 to about 6, and each Y is, independently, a peripheral moiety, comprising the steps of:

• (a) 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;
• (b) 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;
• (c) 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 of peripheral moiety precursors;
• (d) from the working selection set of peripheral moiety precursors choosing a 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, wherein at least about 90% of the combinations of n peripheral moieties derived from said subset have molecular mass sums which are distinct from the molecular mass sums of all other combinations of n peripheral moieties derived from said subset;
• and
• (e) contacting said peripheral moiety precursor subset with a scaffold precursor, said scaffold precursor having n reactive groups, wherein each reactive group is capable of reacting with at least one peripheral moiety precursor to form a covalent bond, under conditions sufficient for the reaction of each reactive group with a peripheral moiety precursor,
• thereby producing a mass-coded set of compounds of the general formula X(Y)n.