Combinatorial synthesis and biomarker development
Provided herein are methods, kits, and compositions for use in the diagnosis and treatment of diseases. Peptoids recognized by Alzheimers disease specific antibodies are identified.
1. A peptoid or pharmaceutically acceptable salt thereof comprising a formula:
or any combination thereof, wherein R is independently selected from a group consisting of a coupling group that couples 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, wherein X is independently selected from oxygen or sulfur; Y is independently selected from deuterium or hydrogen; A is hydrogen, deuterium, aryl, or heteroaryl.
2. The peptoid or pharmaceutically acceptable salt thereof of claim 1 , comprising a structure
3. The peptoid or pharmaceutically acceptable salt thereof of claim 1 , comprising a structure
4. The peptoid or pharmaceutically acceptable salt thereof of claim 1 , comprising a structure
5. The peptoid or pharmaceutically acceptable salt thereof of claim 1 , comprising a structure
6. The peptoid or pharmaceutically acceptable salt thereof of claim 1 , comprising a structure
7. The peptoid or pharmaceutically acceptable salt thereof of claim 1 , comprising a structure
8. The peptoid or pharmaceutically acceptable salt thereof of claim 1 , comprising a structure
9. The peptoid or pharmaceutically acceptable salt thereof of claim 1 , comprising a structure
10. The peptoid or pharmaceutically acceptable salt thereof of claim 1 , comprising a structure
11. A method comprising;
a. contacting a sample with one or more peptoid or pharmaceutically acceptable salt thereof, wherein said one or more peptoid or pharmaceutically acceptable salt thereof comprises a formula:
or any combination thereof, wherein R 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, 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
b. detecting whether or not a molecule is bound to said one or more peptoid or pharmaceutically acceptable salt thereof.
12. 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, wherein said antibody comprises an IgA or a fragment thereof, or an IgM or a fragment thereof wherein said one or more peptoid or pharmaceutically acceptable salt thereof comprises a formula:
or any combination thereof, wherein R 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, 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
b. detecting whether said antibody is bound to said one or more peptoid or pharmaceutically acceptable salt thereof.
13. A method of screening for a biomarker comprising:
a. contacting a control sample with a support having one or more peptoid or pharmaceutically acceptable salt thereof associated with said support, wherein said one or more peptoid or pharmaceutically acceptable salt thereof comprises a formula:
or any combination thereof, wherein R 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, wherein X is independently selected from oxygen or sulfur; Y is independently selected from deuterium or hydrogen; A is hydrogen, deuterium, aryl, or heteroaryl;
b. contacting said support with a disease sample; and
c. detecting said biomarker wherein said biomarker is bound to said one or more peptoid or pharmaceutically acceptable salt thereof and said biomarker is not present in said control sample or said one or more peptoid or pharmaceutically acceptable salt thereof does not bind to said biomarker in said control sample.
14. A method comprising:
a. contacting one or more peptoid or pharmaceutically acceptable salt thereof with a support having at least one biomarker associated with said support, wherein said one or more peptoid or pharmaceutically acceptable salt thereof comprises a formula:
or any combination thereof, wherein R 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, 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
b. detecting said biomarker having said one or more peptoid or pharmaceutically acceptable salt thereof bound thereto.