Neogenesis Drug Discovery, Inc.

Schering Corporation

Neogenesis, Inc.

Edward A Wintner

Seth N Birnbaum

Huw M Nash

Satish Jindal

Krishna Kalghatgi

The present invention provides a method for identifying a member of a mass-coded combinatorial library which is a ligand for biomolecule and assessing the effect of the binding of the ligand to the biomolecule. The mass-coded molecular library comprises compounds of the general formula XY, wherein n is an integer from 2 to about 6, X is a scaffold and each Y is, independently, a peripheral moiety. The mass-coded combinatorial library is produced by reacting a scaffold precursor with a sufficient number of distant peripheral moiety precursors such that there exist at least about 250 distinct combinations of n peripheral moieties derived from the peripheral moiety precursors.

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

The present invention provides an apparatus for producing a mass-coded combinatorial library comprising a set of compounds having the general formula X(Y) , where X is a scaffold, each Y is, independently, a peripheral moiety, and n is an integer greater than 1. The apparatus comprises a digital processor assembly for selecting a peripheral moiety precursor subset from a peripheral moiety precursor set. The subset includes a sufficient number of peripheral moiety precursors that at least about 50 distinct combinations of n peripheral moieties derived from the peripheral moiety precursors in the subset exist. The subset of peripheral moiety precursors is selected so that at least about 90% of all possible combinations of n peripheral moieties derived from the subset have a molecular mass sum which is distinct from the molecular mass sums of all of the other combinations of n peripheral moieties. Methods of use of the mass-coded combinatorial library produced by this apparatus are also disclosed.

The present invention provides a method for producing a mass-coded combinatorial library comprising a set of compounds having the general formula X(Y) , where X is a scaffold, each Y is, independently, a peripheral moiety, and n is an integer greater than 1. The method comprises selecting a peripheral moiety precursor subset from a peripheral moiety precursor set. The subset includes a sufficient number of peripheral moiety precursors that at least about 50 distinct combinations of n peripheral moieties derived from the peripheral moiety precursors in the subset exist. The subset of peripheral moiety precursors is selected so that at least about 90% of all possible combinations of n peripheral moieties derived from the subset have a molecular mass sum which is distinct from the molecular mass sums of all of the other combinations of n peripheral moieties. The method further comprises contacting the peripheral moiety precursor subset with a scaffold precursor which has n reactive groups. Methods of use of the mass-coded combinatorial library produced by this method for identifying a ligand to a particular biomolecule are also disclosed.

The present invention provides a method for producing a mass-coded combinatorial library comprising a set of compounds having the general formula X(Y),, where X is a scaffold, each Y is, independently, a peripheral moiety, and n is an integer greater than 1. The method comprises selecting a peripheral moiety precursor subset from a peripheral moiety precursor set. The subset includes a sufficient number of peripheral moiety precursors that at least about 50 distinct combinations of n peripheral moieties derived from the peripheral moiety precursors in the subset exist. The subset of peripheral moiety precursors is selected so that at least about 90% of all possible combinations of n peripheral moieties derived from the subset have a molecular mass sum which is distinct from the molecular mass sums of all of the other combinations of n peripheral moieties. The method further comprises contacting the peripheral moiety precursor subset with a scaffold precursor which has n reactive groups. Methods of use of the mass-coded combinatorial library produced by this method for identifying a ligand to a particular biomolecule are also disclosed.

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Boston, MA, United States of America

Edward A Wintner