Schering Corporation

Perseptive Biosystems Inc.

Biogen, Incorporated

Neogenesis Drug Discovery, Inc.

Neogenesis, Inc.

Satish Jindal

Huw M Nash

Krishna Kalghatgi

Seth N Birnbaum

Edward A Wintner

Noubar Boghos Afeyan

Sandeep K Paliwal

David Evans

Aruna Pingali

Kevin Williams

Fred E Regnier

Gerald Wayne Shipps, Jr

David R Thomas

Yen-Ming Hsu

Yusheng Liao

Lihong Sun

Zhongli Zheng

Fred B Regnier

Susan Mrose

George R Lenz

Leonid Kirkovsky

Mary-Beth Carter

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 relates to novel CD40:CD154 binding interrupter compounds and use of these compounds and pharmaceutical compositions comprising them, to treat conditions associated with inappropriate CD154 activation in a subject. Specifically, this invention provides compounds which are identified by screening a library of small molecules for those that are capable of specifically binding CD154 and interrupting CD40:CD154 interaction.

CD40:CD154 binding interrupter compounds and use thereof to treat immunological complications

Methods for identifying a member of a mass-coded molecular library, which is a ligand for a biomolecule and binds to the biomolecule at the binding site of a known second ligand for the biomolecule are described. The methods includes contacting a mass-coded molecular library with a biomolecule; separating the biomolecule-ligand complexes from the unbound members of the mass-coded molecular library; contacting the biomolecule-ligand complexes with a second ligand to dissociate biomolecule-ligand complexes in which the ligand binds to the biomolecule at the binding site of the second ligand, thereby forming biomolecule-second ligand complexes and dissociated ligands; separating the dissociated ligands and biomolecule-second ligand complexes; and determining the molecular mass of each dissociated ligand.

The invention provides novel methods for screening a sample to select a ligand to a target of interest and for obtaining information about the ligand and its binding characteristics. Specifically, the claimed multi-dimensional methods involve combining a solution of heterogeneous ligands with the target of interest to screen the ligands on the basis of one or more binding characteristics. Ligands having the first binding characteristic bind to the target of interest thereby to form a target/ligand complex. The complex then optionally is separated from the unbound components using any of a variety of separation techniques, e.g., size exclusion. At least one of the complex or unbound components then is introduced to a second &ldquo;dimension&rdquo;. The second dimension is capable of separating components based upon a second binding characteristic. One then elutes the ligand having the desired binding characteristics.

High speed, automated, continuous flow, multi-dimensional molecular selection and analysis

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.

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

Growing community of inventors

Milton, MA, United States of America

Satish Jindal