COMBINATORIAL SYNTHESIS AND BIOMARKER DEVELOPMENT
Provided herein are methods, kits, and compositions for use in the diagnosis and treatment of diseases. Peptoids recognized by Alzheimer's disease specific antibodies are identified.
1 - 109 . (canceled)
110 . A method comprising:
a. contacting a sample with a non-random peptoid library, wherein said non-random peptoid library comprises one or more peptoid or pharmaceutically acceptable salt thereof having an affinity to an antibody; and
b. detecting whether said antibody is bound to said one or more peptoid or pharmaceutically acceptable salt thereof.
111 . The method of claim 110 , wherein said antibody is bound to said one or more peptoid or pharmaceutically acceptable salt thereof.
112 . The method of claim 111 , wherein said antibody comprises an IgA or a fragment thereof.
113 . The method of claim 111 , wherein said antibody comprises an IgM or a fragment thereof.
114 . The method of claim 111 , wherein said detecting comprise identifying a binding between said one or more peptoid or pharmaceutically acceptable salt thereof and at least two antibody isotypes.
115 . The method of claim 114 , wherein said at least two antibody isotypes comprises at least one of an IgG, IgM, IgD, IgE or an IgA.
116 . The method of claim 111 , wherein the detecting utilizes a method comprising radio immunoassay (“RIA”), fluorescence immunoassay (“FIA”), enzyme-linked immunosorbent assay (“ELISA”), western blot, flow cytometry, Forster resonance energy transfer (“FRET”), surface plasmon resonance, or any combination thereof.
117 . The method of claim 110 , wherein said sample is tissue, cell, urine, serum, whole blood, cerebrospinal fluid, sputum, saliva, or semen.
118 . The method of claim 117 , wherein said sample is serum.
119 . The method of claim 110 , wherein said sample is from a subject suspected of having a disease.
120 . The method of claim 119 , wherein said disease is a neurological disease.
121 . The method of claim 120 , wherein said neurological disease is Parkinson's disease.
122 . The method of claim 120 , wherein said neurological disease is Alzheimer's disease.
123 . The method of claim 110 , wherein said one or more peptoid or pharmaceutically acceptable salt thereof has a binding affinity of at least 10 −5 M (K D ) for said antibody.
124 . The method of claim 110 , wherein said one or more peptoid or pharmaceutically acceptable salt thereof is associated with a support.
125 . The method of claim 124 , wherein there is a linker between said support and said one or more peptoid or pharmaceutically acceptable salt thereof.
126 . The method of claim 125 , wherein said linker comprises a polyethylene glycol (“PEG”) linker.
127 . The method of claim 124 , wherein said solid support is a glass slide, silicon surface, bead, resin or an array.
128 . The method of claim 124 , wherein said solid support is associated with a brush polymer.
129 . The method of claim124, wherein said solid support is associated with a bottle brush polymer.
130 . The method of claim110, further comprising repeating (a) and (b) at different time points to monitor a disease.
131 . The method of claim 110 , wherein said one or more peptoid or pharmaceutically acceptable salt thereof comprises a formula:
wherein R 1 is independently selected from a group consisting of a coupling group capable of coupling to a linker, a substrate, or a label; hydrogen; deuterium; C 1-6 alkyl; C 2-6 alkenyl; C 2-6 alkynyl, C 3-8 cycloalkyl; heteroaryl, cycloalkyl; C 1-6 alkylheteroaryl; C 1-6 alkylaryl; and alkylcycloalkyl; each of which except hydrogen and deuterium may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof;
R 2 is independently selected from a group consisting of hydrogen; deuterium; (CY 2 ) n -aryl; (CY 2 ) n -alkoxyaryl; cycloalkyl; (CY 2 ) n -heteroaryl; and (CY 2 ) n -alkyl; each of which except hydrogen and deuterium may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof;
R 3 is independently selected from a group consisting of (CY 2 ) n -aryl; (CY 2 ) n -alkoxyaryl; alkenyl; alkylaryl; cycloalkyl; alkyldiaryl; and alkyl; each of which may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof;
R 4 is independently selected from a group consisting of (CY 2 ) n -aryl; alkyl; cycloalkyl; and (CY 2 ) n -alkyl; each of which may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof;
R 5 is independently selected from a group consisting of (CY 2 ) n -aryl; (CY 2 ) n -alkyl; alkyl; and alkyldiaryl; each of which may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof;
R 6 is independently selected from a group consisting of alkyldiaryl; alkylaryl; and (CY 2 ) n -alkyl; each of which may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof;
R 7 is independently selected from a group consisting of alkyl; alkylaryl; (CY 2 ) n -aryl; (CY 2 ) n -alkyl; and alkyldiaryl; each of which may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof;
R 8 is independently selected from a group consisting of (CY 2 ) n -heteroaryl; (CY 2 ) n -aryl; alkenyl; (CY 2 ) n -alkyl; alkyl; and alkyldiaryl; each of which may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof;
R 9 is independently selected from a group consisting of alkylaryl; (CY 2 ) n -aryl; alkyldiaryl; and (CY 2 ) n -alkyl; each of which may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof;
R 10 is independently selected from a group consisting of (CY 2 ) n -aryl; alkyl; (CY 2 ) n -alkyl; and (CY 2 ) n -heteroaryl; each of which may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof;
R 11 is independently selected from a group consisting of hydrogen; deuterium; C 1-6 alkyl; C 2-6 alkenyl; C 2-6 alkynyl, C 3-8 cycloalkyl; heteroaryl, cycloalkyl; C 1-6 alkylheteroaryl; C 1-6 alkylaryl; and alkylcycloalkyl; each of which except hydrogen and deuterium may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof;
R 12 is independently selected from a group consisting of a coupling group capable of coupling to a linker, a substrate, or a label; hydrogen; deuterium; C 1-6 alkyl; C 2-6 alkenyl; C 2-6 alkynyl, C 3-8 cycloalkyl; heteroaryl, cycloalkyl; C 1-6 alkylheteroaryl; C 1-6 alkylaryl; and alkylcycloalkyl; each of which except hydrogen and deuterium may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof;
R 13 is individually and independently selected from a group consisting of hydrogen; deuterium; a halogen; ethyl; and methyl; wherein when R 13 is not hydrogen each carbon denoted with an * can independent be R or S; wherein X is independently selected from oxygen or sulfur; Y is independently selected from deuterium or hydrogen; A is hydrogen, deuterium, aryl, or heteroaryl and n is 1-10.