Nucleotides and analogs having photoremovable protecting groups
First Claim
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1. A reactor system for synthesizing a plurality of polymer sequences on a substrate comprising:
- a) a reactor for contacting reaction fluids to said substrate;
b) a system for delivering selected reaction fluids to said reactor;
c) a translation stage for moving a mask or substrate from at least a first relative location relative to a second relative location;
d) a light for illuminating said substrate through a mask at selected times; and
e) an appropriately programmed digital computer for selectively directing a flow of fluids from said reactor system, selectively activating said translation stage, and selectively illuminating said substrate so as to form a plurality of diverse polymer sequences on said substrate at predetermined locations.
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Abstract
A synthetic strategy for the creation of large scale chemical diversity. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis. Binary masking techniques are utilized in one embodiment. A reactor system, photoremovable protective groups, and improved data collection and handling techniques are also disclosed. A technique for screening linker molecules is also provided.
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Citations
56 Claims
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1. A reactor system for synthesizing a plurality of polymer sequences on a substrate comprising:
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a) a reactor for contacting reaction fluids to said substrate;
b) a system for delivering selected reaction fluids to said reactor;
c) a translation stage for moving a mask or substrate from at least a first relative location relative to a second relative location;
d) a light for illuminating said substrate through a mask at selected times; and
e) an appropriately programmed digital computer for selectively directing a flow of fluids from said reactor system, selectively activating said translation stage, and selectively illuminating said substrate so as to form a plurality of diverse polymer sequences on said substrate at predetermined locations. - View Dependent Claims (2)
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- 3. An ordered method for forming a plurality of polymer sequences by sequential addition of reagents comprising the step of serially protecting and deprotecting portions of said plurality of polymer sequences for addition of other portions of said polymer sequences using a binary synthesis strategy.
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17. A method of screening a plurality of linker polymers for use in binding affinity studies comprising the steps of:
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a) forming a plurality of linker polymers on a substrate in selected regions, said linker polymers formed by the steps of recursively;
i) on a surface of a substrate, irradiating a portion of said selected regions to remove a protective group; and
ii) contacting said surface with a monomer;
b) contacting said plurality of linker polymers with a ligand; and
c) contacting said ligand with a labeled receptor. - View Dependent Claims (18, 19, 20, 21)
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22. A system for determining affinity of a receptor to a ligand comprising:
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a) means for applying light to a surface of a substrate, said substrate comprising a plurality of ligands at predetermined locations, said means for applying directing light providing simultaneous illumination at a plurality of said predetermined locations; and
b) an array of detectors for detecting light fluoresced at said plurality of predetermined locations. - View Dependent Claims (23, 24, 25)
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26. In a digital computer, a method of determining the tendency of a receptor to bind to a ligand comprising:
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a) exposing fluorescently labelled receptors to a substrate, said substrate comprising a plurality of ligands in regions at known locations;
b) at a plurality of data collection points within each of said regions, determining an amount of light fluoresced from said data collection points;
c) removing said data collection points deviating from a preset amount from a predetermined statistical distribution; and
d) determining a relative binding affinity of said receptor to remaining data collection points. - View Dependent Claims (27)
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- 28. A compound having the formula:
- 38. A compound having the formula:
- 42. A compound having the formula:
- 46. A compound having the formula:
- 50. A compound having the formula:
Specification