Mass-based encoding and qualitative analysis of combinatorial libraries
AssigneeSmithKline Beecham Corporation
InventorsHendrik Mario Geysen, Daniel Stuart Kinder, Craig Daniel Wagner
Life of this patent
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Abstract
The insertion of isotopically labeled portions into solid state combinatorial synthesis constructs followed by mass spectrometer, mass-based nuclear magnetic resonance spectrometry or mass-based infrared spectrometry analysis allows for the physical, non-chemical encoding of large numbers of combinatorial synthesis products.
Claims22
A method for labeling a plurality of solid supports, said method comprising;
- dividing a batch of solid supports that each have a first link having a first cleavage site into two or more groups of solid supports;
- preparing a mixture of chemical moieties that are distinguishable from each other by mass to produce a set of machine readable codes;
- chemically labeling each solid support group with one of the codes of the set under controlled reaction conditions such that each solid support group is labeled with a different code that is attached to the first link;
- linking a second link having a second cleavage site and a synthesis site to each code on the solid support to provide a set of constructs that each have a connecting group comprising in series the first cleavage site, the machine-readable code, the second cleavage site, and the synthesis site, wherein the formula of the connecting group is:
- L1-C-L2 where L1 is the first cleavage site, C is the code and L2 is the second cleavage site;
- selecting at least some of the solid supports having the connecting group L1-C-L2 from the batch;
- and
- reading the machine readable code of the selected solid supports.
The method as claimed in clam 1, wherein said reading step is automated.
A method for labeling a plurality of solid supports to determine chemical reagents synthesized to the solid supports, said method comprising:
- dividing a batch of solid supports that each have a first link having a first cleavage site into two more groups of solid supports;
- preparing a mixture of chemical moieties that are distinguishable from each other by mass to produce a set of machine readable codes;
- chemically labeling each solid support group with one of the codes of the set under controlled reaction conditions such that each solid support group is labeled with a different code that is attached to the first link;
- linking a second link having a second cleavage site and a synthesis site to each code on the solid support to provide a set of constructs that each have a connecting group comprising in jenies the first cleavage site, the machine-readable code, the second cleavage site, and the synthesis site, wherein the formula of the connecting group is;
- L1-C-L2 where L1 is the first cleavage site, C is the code and L2 is the second cleavage site, wherein the chemical moieties are isotropically doped and are mixed with one another in a plurality of discrete ratios;
- subjecting the solid supports having the connecting group L1-C-L2 of each solid support group of the batch to a first chemical reagent;
- optionally combining two or more of the groups of the solid supports having the connecting group L1-C-L2 into a combined group of solid supports and then subjecting the combined group of solid supports to a second chemical reagent;
- selecting at least some of the solid supports from the combined group of solid supports;
- and
- reading the machine readable code of the selected solid supports to determine the first chemical reagent to which the solid supports were subjected.
Dependencies are inferred from the claim text.