Microarray having a chemical library of compounds
A microarray and a process for making the microarray having a library of chemical compounds are disclosed herein. Each member of the library is attached at a known location. The microarray has a plurality of addressable electrodes and a porous reaction layer attached to each electrode. The porous reaction layer has reactive hydroxyl groups. Michael acceptors are attached to the porous reaction layer of selected electrodes. The Michael acceptors are attached at the hydroxyl groups using electrochemically-generated base that is generated by the selected electrodes and confined to the selected electrodes with the use of excess activated ester. At least one of a plurality of chemical compounds from a library of compounds is attached to the olefin of the plurality of Michael acceptors. Attachment occurs only at the selected electrodes having Michael acceptors with unreacted olefin. Each member of the library of compounds is attached to the known locations.
1 . A process for making a microarray having a library of chemical compounds that are attached at known locations on the microarray, comprising:
(a) providing a microarray having addressable electrodes, wherein a porous reaction layer is attached to each one of the addressable electrodes, wherein the porous reaction layer that is attached to each one of the addressable electrodes is a known location, wherein the porous reaction layer has hydroxyl groups;
(b) attaching a Michael acceptor having an attaching group to one of the known locations by a base-catalyzed chemical reaction that occurs at the hydroxyl groups, wherein the base for the base-catalyzed chemical reaction is an electrochemically-generated base that is generated by activating the addressable electrode at the known location, wherein the electrochemically-generated base is confined to a region surrounding the addressable electrode at the known location using a scavenging agent;
(c) attaching a chemical compound from a chemical library to the olefin of the Michael acceptor that is attached to one of the known locations; and
(d) repeating steps (b) through (c) until each member of the chemical library is attached to at least one of the known locations.
2 . The process of claim 1 , wherein the attaching group is an activated ester and the base-catalyzed chemical reaction attaching the Michael acceptor is an esterification reaction of the activated ester, wherein the activated ester attached to the Michael acceptor acts as the scavenging agent, wherein the activated ester is activated by a chemical selected from the group consisting of succinimide, pentafluorophenol, para-nitrophenol, and hydroxy-benztriazole and combinations thereof.
3 . The process of claim 1 , wherein the attaching group is selected from the group consisting of acid fluoride, acid anhydride, and imidazolate and combinations thereof, wherein the attaching group attached to the Michael acceptor acts as the scavenging agent.
4 . The process of claim 1 , wherein the scavenging agent is
wherein X is a leaving group selected from the group consisting of fluoride, chloride, bromide, iodide, anhydride, imidazolate, and R 2 O—, and combinations thereof, wherein R 1 is selected from the group consisting of alkyl, alkenyl, alkynyl, and aryl and combinations thereof, wherein R 2 is selected from the group consisting of succinimide, pentafluorophenyl, para-nitrophenyl, and benztriazole and combinations thereof.
5 . The process of claim 1 , wherein the olefin of the Michael acceptors is selected from the group consisting of ethylene and maleimide and combinations thereof.
6 . The process of claim 1 , wherein the Michael acceptors are selected from the group consisting of N-succinimidyl 3-maleimidopropioate, N-succinimidyl 6-maleimidocaproate, and N-acryloxysuccinimide and combinations thereof.
7 . The process of claim 1 , wherein the step of attaching a chemical compound from a chemical library to the olefin of the Michael acceptor that is attached to one of the known locations, further comprises: attaching using chemical base or electrochemically-generated base that is generated by activating the addressable electrode at the known location.
8 . The process of claim 1 , wherein each of the chemical compounds from the chemical library has a thiol group, wherein the thiol group reacts with the olefin of the Michael acceptors, whereby the chemical compounds from the chemical library are attached to the Michael acceptors through a sulfide linkage.
9 . The process of claim 1 , wherein the chemical library is selected from the group consisting of peptides, peptidomimetics, proteins, DNA, RNA, small molecule drug candidates, diversity oriented synthesis products, and functionalized members of the foregoing and combinations thereof.
10 . A microarray having a library of chemical compounds that are attached at known locations on the microarray, comprising:
(a) a microarray having addressable electrodes, wherein a porous reaction layer is attached to each one of the addressable electrodes, wherein the porous reaction layer that is attached to each one of the addressable electrodes is a known location, wherein the porous reaction layer has hydroxyl groups;
(b) Michael acceptors having an attaching group and attached to each one of the known locations by a base-catalyzed chemical reaction that occurs at the hydroxyl groups, wherein the base for the base-catalyzed chemical reaction is an electrochemically-generated base that is generated by activating the addressable electrode at the known location, wherein the electrochemically-generated base is confined to a region surrounding the addressable electrode at the known location using a scavenging agent; and
(c) a chemical compound from a chemical library attached to the olefin of each one of the Michael acceptors.
11 . The microarray of claim 10 , wherein the attaching group is an activated ester and the base-catalyzed chemical reaction attaching the Michael acceptors is an esterification reaction of the activated ester, wherein the activated ester attached to the Michael acceptor acts as the scavenging agent, wherein the activated ester is activated by a chemical selected from the group consisting of succinimide, pentafluorophenol, para-nitrophenol, and hydroxy-benztriazole and combinations thereof.
12 . The microarray of claim 10 , wherein the attaching group is selected from the group consisting of acid fluoride, acid anhydride, and imidazolate and combinations thereof, wherein the attaching group attached to the Michael acceptor acts as the scavenging agent.
13 . The microarray of claim 10 , wherein the scavenging agent is
wherein X is a leaving group selected from the group consisting of fluoride, chloride, bromide, iodide, anhydride, imidazolate, and R 2 O—, and combinations thereof, wherein R 1 is selected from the group consisting of alkyl, alkenyl, alkynyl, and aryl and combinations thereof, wherein R 2 is selected from the group consisting of succinimide, pentafluorophenyl, para-nitrophenyl, and benztriazole and combinations thereof.
14 . The microarray of claim 10 , wherein the olefin of the Michael acceptors is selected from the group consisting of ethylene and maleimide and combinations thereof.
15 . The microarray of claim 10 , wherein the Michael acceptors are selected from the group consisting of N-succinimidyl 3-male-imidopropioate, N-succinimidyl 6-maleimidocaproate, and N-acryloxysuccinimide and combinations thereof.
16 . The microarray of claim 10 , wherein the chemical compounds from the chemical library are attached using chemical base or electrochemically-generated base that is generated by activating the addressable electrode at the known location.
17 . The microarray of claim 10 , wherein each of the chemical compounds from the chemical library has a thiol group, wherein the thiol group reacts with the olefin of the Michael acceptors, whereby the chemical compounds from the chemical library are attached to the Michael acceptors through a sulfide linkage.
18 . The microarray of claim 10 , wherein the chemical library is selected from the group consisting of peptides, peptidomimetics, proteins, DNA, RNA, small molecule drug candidates, diversity oriented synthesis products, and functionalized members of the foregoing and combinations thereof.