Large scale photolithographic solid phase synthesis of an array of polymers

Claim 1

A method of forming an array of diverse peptides on a substrate, the surface of said substrate comprising at least first and second regions having peptide molecules thereon, said peptide molecules coupled to a photoremovable protective group at a first functional group, said first functional group capable of binding to a second functional group of selected amino acids which also have a first functional group coupled to a photoremovable protective group, said method comprising the steps of: removing said photoremovable protective group from said peptide molecules in said first region of said substrate with light to expose said first functional group, but not removing said photoremovable protective group from said peptide molecules in said second region; contacting said first and second regions of said surface with first selected amino acid molecules to covalently bond said second functional group of said first amino acid molecules to said first functional group of said peptides by means of a peptide bond in said first region, but not said second region; removing the photoremovable protective group from at least a portion of said first selected amino acid molecules in said first region with light to expose said first functional group on said at least a portion of said first selected amino acid molecules; and contacting said first and said second regions with second selected amino acid molecules to covalently bond a second functional group of said second selected amino acid molecules to said first functional group of said first selected amino acid molecules by means of a peptide bond, forming peptides in said first region having a different amino acid sequence than peptides in said second region.

Claim 2

A method of forming an array of diverse peptides on a substrate, the surface of said substrate comprising at least first and second regions having peptide molecules thereon, said peptide molecules coupled to a photoremovable protective group at a first functional group, said first functional group capable of binding to a second functional group of selected amino acids which also have a first functional group coupled to a photoremovable protective group, said method comprising the steps of: removing said photoremovable protective group from said peptide molecules in said first region of said substrate with light to expose said first functional group, but not removing said photoremovable protective group from said peptide molecules in said second region; contacting said first and second regions of said surface with first selected amino acid molecules to covalently bond said second functional group of said first amino acid molecules to said first functional group of said peptides by means of a peptide bond in said first region, but not said second region; removing the photoremovable protective group from at least a portion of said first selected amino acid molecules in said first region with light to expose said first functional group on said at least a portion of said first selected amino acid molecules; and contacting said first and said second regions with second selected amino acid molecules to covalently bond a second functional group of said second selected amino acid molecules to said first functional group of said first selected amino acid molecules by means of a peptide bond, forming peptides in said first region having a different amino acid sequence than peptides in said second region.

Claim 13

A method of making an array comprising at least two different peptides immobilized on a substrate, wherein said peptides differ from one another with respect to monomer sequence, by synthesizing said peptides on a surface of said substrate, said surface having functional groups capable of coupling with an amino acid, said functional groups protected by photoremovable protecting groups, said method comprising the steps of: selectively activating said surface by removing said photoremovable protecting groups from said functional groups with light so that a first pattern of activated and unactivated regions is formed on said surface; contacting said surface with a first amino acid, said first amino acid having at least a first functional group capable of coupling with said functional groups in said activated regions of said surface and a second functional group capable of coupling with another amino acid, said second functional group protected by a photoremovable protecting group, under conditions such that said first amino acid is coupled to said functional groups in said activated regions by means of a peptide bond; selectively activating said surface by removing said photoremovable protecting groups from said functional groups with light so that a second pattern of activated and unactivated regions is formed on said surface; contacting said surface with a second amino acid, said second amino acid having at least a first functional group capable of coupling with said functional groups in said activated regions of said surface and a second functional group capable of coupling with another amino acid, said second functional group protected by a photoremovable protecting group, under conditions such that said second amino acid is coupled to said functional groups in said activated regions by means of a peptide bond; and repeating said activating and coupling steps until said two different peptides are formed on said surface, so that each different peptide is present at a defined location on said surface and has a defined amino acid sequence, whereby the amino acid sequence and location of each different polymer is defined by the patterns of activated and unactivated regions formed during each activating step and the monomers coupled in each coupling step.

Claim 14

A method of making an array comprising at least two different peptides immobilized on a substrate, wherein said peptides differ from one another with respect to monomer sequence, by synthesizing said peptides on a surface of said substrate, said surface having functional groups capable of coupling with an amino acid, said functional groups protected by photoremovable protecting groups, said method comprising the steps of: selectively activating said surface by removing said photoremovable protecting groups from said functional groups with light so that a first pattern of activated and unactivated regions is formed on said surface; contacting said surface with a first amino acid, said first amino acid having at least a first functional group capable of coupling with said functional groups in said activated regions of said surface and a second functional group capable of coupling with another amino acid, said second functional group protected by a photoremovable protecting group, under conditions such that said first amino acid is coupled to said functional groups in said activated regions by means of a peptide bond; selectively activating said surface by removing said photoremovable protecting groups from said functional groups with light so that a second pattern of activated and unactivated regions is formed on said surface; contacting said surface with a second amino acid, said second amino acid having at least a first functional group capable of coupling with said functional groups in said activated regions of said surface and a second functional group capable of coupling with another amino acid, said second functional group protected by a photoremovable protecting group, under conditions such that said second amino acid is coupled to said functional groups in said activated regions by means of a peptide bond; and repeating said activating and coupling steps until said two different peptides are formed on said surface, so that each different peptide is present at a defined location on said surface and has a defined amino acid sequence, whereby the amino acid sequence and location of each different polymer is defined by the patterns of activated and unactivated regions formed during each activating step and the monomers coupled in each coupling step.