METHOD AND APPARATUS FOR COMBINATORIAL CHEMISTRY
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Abstract
A method and apparatus are provided for performing light-directed reactions in spatially addressable channels within a plurality of channels. One aspect of the invention employs photoactivatable reagents in solutions disposed into spatially addressable flow streams to control the parallel synthesis of molecules immobilized within the channels. The reagents may be photoactivated within a subset of channels at the site of immobilized substrate molecules or at a light-addressable site upstream from the substrate molecules. The method and apparatus of the invention find particularly utility in the synthesis of biopolymer arrays, e.g., oligonucleotides, peptides and carbohydrates, and in the combinatorial synthesis of small molecule arrays for drug discovery.
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Citations
62 Claims
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1-8. -8. (canceled)
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10-47. -47. (canceled)
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48. A method for detritylation of oligonucleotides comprising the steps of:
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contacting terminally-protected oligonucleotides with a solution comprising a carboxylic acid, wherein the carboxyl group of the acid is protected with a photolabile protecting group; and exposing the solution to a radiation source sufficient to cause deprotection of the carboxylic acid to provide an acid compound for detritylating the terminally-protected oligonucleotides. - View Dependent Claims (9, 49, 50, 51)
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52. A method for the detritylation of oligonucleotides comprising the steps of:
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exposing a precursor solution comprising a carboxylic acid, wherein the carboxyl group of the acid is protected with a photolabile protecting group, to a radiation source sufficient to cause deprotection of the carboxyl group; and contacting terminally-protected oligonucleotides with the irradiated precursor solution for a period of time sufficient to cause detritylation of the oligonucleotides. - View Dependent Claims (53, 54, 55, 56)
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57. A method for detritylation of oligonucleotides comprising the steps of:
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contacting terminally-protected oligonucleotides with an acid precursor solution comprising a phenolic compound; and exposing the precursor solution to a radiation source sufficient to cause increased acidity of the precursor solution for detritylating the terminally-protected oligonucleotides. - View Dependent Claims (58, 59)
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60. A method for the detritylation of oligonucleotides comprising the steps of:
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exposing a precursor solution comprising a phenolic compound to a radiation source sufficient to increase an acidity of the phenolic compound sufficient to provide an acid for detritylating terminally-protected oligonucleotides; and contacting terminally-protected oligonucleotides with the irradiated precursor solution for a period of time sufficient to cause detritylation of the oligonucleotides. - View Dependent Claims (61, 62)
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Specification