Method for selecting a chemical entity from a tagged library
First Claim
1. In a method of determining the identity of a chemical entity in a combinatorial library comprising a plurality of structurally distinct chemical entities,wherein the chemical entities are non-polymeric compounds,wherein each chemical entity is tagged with an entity tag identifying the structure of the chemical entity,wherein each chemical entity comprises a plurality of fragments,wherein the entity tag consists essentially of a plurality of fragment tags, each fragment tag identifying one of the fragments constituting a fragment of the chemical entity tagged by said entity tag,wherein the identity of at least one chemical entity is determined from the entity tag with which it is tagged,the improvement comprisingligating at least one pair of fragment tags by enzyme-catalysed ligation.
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Abstract
Disclosed is a method for determining the identity of a chemical entity having a preselected property. The chemical entity is identified from a library composed of a plurality of different chemical entities each appended to unique identifier tags. An anti-tag having the capability of specifically interacting with the unique identifier tag is recovered during the method and used for identification purposes.
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Citations
61 Claims
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1. In a method of determining the identity of a chemical entity in a combinatorial library comprising a plurality of structurally distinct chemical entities,
wherein the chemical entities are non-polymeric compounds, wherein each chemical entity is tagged with an entity tag identifying the structure of the chemical entity, wherein each chemical entity comprises a plurality of fragments, wherein the entity tag consists essentially of a plurality of fragment tags, each fragment tag identifying one of the fragments constituting a fragment of the chemical entity tagged by said entity tag, wherein the identity of at least one chemical entity is determined from the entity tag with which it is tagged, the improvement comprising ligating at least one pair of fragment tags by enzyme-catalysed ligation.
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61. In a method of determining the identity of a chemical entity in a combinatorial library comprising a plurality of structurally distinct chemical entities,
wherein each chemical entity is tagged with an entity tag identifying the structure of the chemical entity, wherein each chemical entity comprises a plurality of fragments, wherein the entity tag consists essentially of a plurality of fragment tags, each fragment tag identifying one of the fragments constituting a fragment of the chemical entity tagged by said entity tag, wherein the identity of at least one chemical entity is determined from the entity tag with which it is tagged, wherein the entity tags of the combinatorial library are oligonucleotides, wherein, prior to generating the combinatorial library comprising a plurality of structurally distinct chemical entities, an initial, oligonucleotide tagged combinatorial library of chemical entity fragments is generated by appending a different identifier oligonucleotide tag fragment to each of a plurality of different chemical entity fragments, wherein each different identifier oligonucleotide tag fragment identifies a different chemical entity fragment, wherein the initial, oligonucleotide tagged combinatorial library of chemical entity fragments is subjected to a condition for partitioning, wherein a subset of chemical entity fragments having a predetermined property is partitioned from the remainder of the initial, oligonucleotide tagged combinatorial library of chemical entity fragments, thereby generating a partitioned oligonucleotide tagged library of chemical entity fragments, wherein the partitioned oligonucleotide tagged library of chemical entity fragments is subjected to further tag, fragment enzyme-catalysed ligation steps and further chemical entity fragment reaction steps, thereby generating the oligonucleotide tagged combinatorial library of structurally distinct chemical entities, wherein the oligonucleotide tagged combinatorial library of chemical entities is subjected to a condition for partitioning, wherein a subset of chemical entities having a predetermined property is partitioned from the remainder of the oligonucleotide tagged combinatorial library of structurally distinct chemical entities, thereby generating a partitioned oligonucleotide tagged library of structurally distinct chemical entities, wherein identifier oligonucleotides appended to one or more partitioned, chemical entities having the predetermined property are recovered, wherein said recovered identifier oligonucleotides identifies in a specific manner the one or more partitioned chemical entities, and wherein the chemical entities having the predetermined property are identified by decoding the recovered identifier oligonucleotides identifying the one or more partitioned chemical entities, the improvement comprising ligating at least one pair of fragment tags by enzyme-catalysed ligation.
Specification