Compositions for detecting or measuring an analyte

Abstract

The present invention relates to a composition for detecting or measuring an analyte and an analytical method using said composition. In particular, the composition and analytical method of the present invention can greatly improve the efficiency and performance of sample analysis.

Description

[Technical field]

[0001] The present invention relates to a composition for detecting or measuring an analyte, a kit containing the same, and a method for detecting or measuring an analyte using the same. [Background technology]

[0002] Methods for detecting or measuring analytes in biological samples include protein chip analysis, immunoassays, ligand binding assays, radioimmunoassays, radial immunodiffusion, Ouchterlony immunodiffusion, rocket immunoelectrophoresis, tissue immunostaining, complement fixation assays, 2D electrophoresis, Western blotting, and ELISA and mass spectrometry, while methods for quantifying genetic material include reverse transcription polymerase chain reaction (RT-PCR), competitive RT-PCR, real-time RT-PCR, RNase protection assay (RPA), Northern blotting, DNA chips, etc.

[0003] Among these, mass spectrometry (MS) is an analytical technique that can selectively separate, detect, and quantify specific analytes in biological samples based on the specific mass-to-charge ratio (m / z) of the substance, and monitor changes in their concentration. This type of mass spectrometry is a highly selective and sensitive analytical method that can detect only information on the target components.

[0004] However, since there is no amplification mechanism for amino acids in the detection and quantification process of substances composed of amino acids such as proteins, no matter how sensitive the mass spectrometer is, it is not possible to analyze trace amounts of substances below the detection limit, and the speed at which large amounts of samples are analyzed is also slow.

[0005] In addition, in mass spectrometry, when the analyte has a complex three-dimensional structure such as a protein, it is fragmented into peptide fragments through a digestion reaction and only the mass-to-charge ratio (m / z) of a specific peptide is measured. During this process, many unnecessary peptides are also absorbed into the analyte, generating noise and acting as a factor that reduces sensitivity.

[0006] Therefore, there is a need for a method that can omit the above steps while still allowing highly sensitive quantification of an analyte in a biological sample, shortening the analysis time, and improving the convenience of the analysis. Summary of the Invention [Problem to be solved by the invention]

[0007] One object of the present invention is to provide compositions and kits containing the same for detecting or measuring an analyte.

[0008] Another object of the present invention seeks to provide a method for detecting or measuring an analyte.

[0009] However, the technical problems that the present invention aims to solve are not limited to those mentioned above, and other problems not mentioned will be clearly understood by those having ordinary skill in the art from the following description. [Means for solving the problem]

[0010] Various embodiments described herein will be described below with reference to the drawings. In the following description, various specific details, such as specific configurations, compositions, and steps, are described in order to fully understand the present invention. However, certain embodiments can be practiced without one or more of these specific details, or with other known methods and configurations. In other instances, known processes and manufacturing techniques are not described in specific detail so as not to unnecessarily obscure the present invention. References throughout this specification to "one embodiment" or "embodiments" mean that a particular feature, configuration, composition, or characteristic described in connection with an embodiment is included in one or more embodiments of the present invention. Thus, the appearance of "in one embodiment" or "embodiments" in various places throughout this specification does not necessarily refer to the same embodiment of the present invention. Additionally, particular features, configurations, compositions, or characteristics may be combined in any suitable manner in one or more embodiments. Unless otherwise defined within the present specification, all scientific and technical terms used herein have the same meaning as commonly understood by those skilled in the art to which the present invention pertains.

[0011] According to one embodiment of the present invention, there is provided a composition for the detection or measurement of an analyte, comprising a conjugate compound of formula 1:

number

[0012] In the present invention, the "analyte" refers to a substance present in a sample or solution that is the subject of analysis. In particular, in the present invention, the "analyte" may be a substance present in a biological sample, and may include any one or more selected from the group consisting of proteins, lipoproteins, glycoproteins, DNA, and RNA, but is not limited to such a substance as long as it is a molecule in the body that contains organic substances such as amino acids, nucleotides, monosaccharides, or lipids as monomers.

[0013] In the present invention, the M is not particularly limited in type as long as it is a repeatable unit compound that can be detected or measured in place of an analyte, but preferably, the mass-to-charge ratio (m / z) of the M may be 30 to 3000. When the mass-to-charge ratio (m / z) of the M is 30 to 3000, it has the effect of being easily analyzed by a mass spectrometer.

[0014] In the present invention, the term "monomer" refers to a compound that serves as a unit for synthesizing a polymer, and the type thereof is not particularly limited, and may be, for example, an amino acid, an amino acid analog, a peptide, a peptide analog, a monosaccharide, an oligosaccharide, or a polysaccharide.

[0015] In the present invention, the term "amino acid" refers to a compound having a basic amino group (-NH 2 ), an acidic carboxyl group (-COOH) and a side chain (-R group) are bonded, and any amino acid capable of forming a peptide bond is included without limitation. Thus, the amino acids include all amino acids derived from living organisms or artificially synthesized, and their constituent elements are not limited to carbon, hydrogen, oxygen, nitrogen, sulfur, etc., but may additionally contain other elements and may include all forms of isomers. Of the amino acids, 20 types are encoded by the genes of eukaryotes and prokaryotes, but more than 500 types are known to occur in nature.

[0016] In the present invention, the term "amino acid analog" refers to an amino acid that can be used to crosslink peptides or protein complexes by forming a peptide bond in place of an amino acid and has an amino group (-NH 2 ) and those having a carboxyl group (-COOH) are included without limitation.

[0017] In the present invention, the amino acid may be glycine, alanine, valine, leucine, isoleucine, threonine, serine, cysteine, methionine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, arginine, histidine, phenylalanine, tyrosine, tryptophan, proline, pyrrolysine, theanine, gamma-glutamylmethylamide, beta-aminobutyric acid, or gamma-aminobutyric acid; or an isomer thereof, and preferably, any one or more selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, threonine, serine, cysteine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, arginine, phenylalanine, tyrosine, tryptophan, and proline, but is not limited thereto.

[0018] In formula 1, n is preferably an integer of 2 to 50,000, more preferably an integer of 2 to 10,000, even more preferably an integer of 2 to 5,000, even more preferably an integer of 2 to 1,000, and most preferably an integer of 2 to 100.

[0019] According to another embodiment of the present invention, in formula 1, n is an integer from 101 to 100,000, preferably an integer from 101 to 50,000, more preferably an integer from 101 to 10,000, even more preferably an integer from 101 to 5,000, and most preferably an integer from 101 to 1,000.

[0020] In the present invention, the amino acid analogue is a compound in which the carboxyl group (-COOH) and the amino group (NH 2It may also be a compound in which a protecting group is added to the functional group excluding (-). Non-limiting examples include (Fmoc-Cys-OtBu)2, (H-Cys-OH)2, (H-Cys-OMe)2·2HCl, (H-HoCys-OH)2, (R)-N-Fmoc-2-(7-octenyl)Alanine, (S)-N-Fmoc-α-(4-pentenyl)Alanine, (Z-Cys-OH)2, 3-Cyclopentane-D-Alanine, 3-Methoxy-2-nitropyridine, 5-Ethyltio-1H-Tetrazole, 6-Fmoc-Acp-ol, 8-Aoc-OH·HCl, 9-Fluorenylmethanol, Ac-2-Nal-OH, Ac-Ala-OH, Ac-Ala-OMe, Ac-Arg-OH, Ac-Arg-OH·2H2O, Ac-Asp(OtBu)-OH, Ac-Asp-OH, Ac-Asp-OtBu, Ac-Cys(Me)-OH, Ac-Cys(Trt)-OH, Ac-Cys-OH, Ac-D-2-Nal-OH, Ac-D-Ala-OH, Ac-D-Allo-Ile-OH, Ac-Dap(Boc)-OH, Ac-D-Arg(Pbf)-OH, Ac-D-Arg-OH, Ac-D-Asn(Trt)-OH, Ac-D-Asp(OtBu)-OH, Ac-D-Cys(Trt)-OH, Ac-D-Gln(Trt)-OH, Ac-D-Glu(OtBu)-OH, Ac-D-Glu-OH, Ac-D-His(Trt)-OH, Ac-DL-Abu-OH, Ac-DL-Ala-OH, Ac-D-Phe(2-Br)-OH, Ac-D-Phe(3-F)-OH, Ac-D-Phe(4-Br)-OH, Ac-D-Phe-OH, Ac-D-Pro-OH, Ac-D-Ser(tBu)-OH, Ac-D-Thr(tBu)-OH, Ac-D-Trp(Boc)-OH, Ac-D-Trp-OH, Ac-D-Tyr(tBu)-OH, Ac-D-Val-OH, Ac-Gln-OH, Ac-Gln-OtBu, Ac-Glu(OtBu)-OH, Ac-Gly-Gly-OH, Ac-Gly-OEt, Ac-Gly-OH, Ac-His(Trt)-OH, Ac-His-OH·H2O, Ac-HMBA-linker, Ac-HoPhe-OH, Ac-Ile-OH, Ac-Leu-OH, Ac-Lys(Ac)-OH·DCHA,Ac-Lys(Boc)-OH、Ac-Lys(Fmoc)-OH、Ac-Lys(Z)-OH、Ac-Lys-OMe·HCl、Ac- Met-OH、Ac-Nle-OH、Ac-Nva-OH、Ac-Orn-OH、Ac-Phe-OH、Ac-Phg(4-OAc)-OH 、Ac-Phg(4-OH)-OEt、Ac-Pro-OH、Ac-Ser(tBu)-OH、Ac-Thr(tBu)-OH、Ac-T rp(Boc)-OH、Ac-Trp-NH2、Ac-Trp-OEt、Ac-Trp-OH、Ac-Trp-OMe、Ac-Tyr(3, 5-DiNO2)-OH、Ac-Tyr(Ac)-OH、Ac-Tyr(tBu)-OH、Ac-Tyr-OEt·H2O、Ac-Tyr -OH、Ac-Tyr-OMe、Ac-Val-OH、Ac-β-Ala-OH·DCHA、Alloc-D-Met-OH·DCHA、A lloc-Gly-OH、Alloc-Gly-OH·DCHA、Alloc-Leu-OH、Alloc-Leu-OH·DCHA、Alloc-Lys(Fmoc)-OH、Allo-Thr-OH、Beta-Ala-Gly-Him、Boc-OH、N -2-Abz-OH、Boc-2-Nal-OH、Boc-2-Pal-OH、Boc-3-Pal-OH、Boc-4-Abz-OH、Boc-4-Amb-OH、Boc-4-Amc-OH、Boc-4-oxo、Pro-Boc-OH c-4-Pal-OH、Boc-5-Ava-OH、Boc-8-Aoc-OH、Boc-Abu-OH、Boc-Abu-OH·DCHA、Boc-Aib-OH、Boc-Aib-ol、Boc-Ala-NH2、cBo、ABoc-OHlan -Ala-ONp、Boc-Ala-OSu、Boc-Aoa-OH、Boc-Arg(Mts)-OH、Boc-Arg(Mts)-O H·CHA、Boc-Arg(NO2)-OH、Boc-Arg(Pbf)-OH、Boc-Arg(Pbf)-OH·CHA、Boc-A rg(Cos)-OH、Boc-Arg(Z)-OH、Boc-Arg-OH、Boc-Arg-OH·HCl·H2O、Boc-Arg- pNA·HCl、Boc-Asn(Trt)-OH、Boc-Asn(Xan)-OH、Boc-Asn-OH、Boc-Asn-ONp、Boc-Asp(OBzl)-OH、Boc-Asp(OBzl)-ONp、Boc-Asp(OBzl)-OSu、Boc-Asp(OcHex)-OH、Boc-Asp(OFm)-OH、Boc-Asp(OMe)-OH、Boc-Asp(OMe)-OH·DCHA、Boc-Asp(OtBu)-OH、Boc-Asp(OtBu)-OH·DCHA、Boc-Asp(OtBu)-ONp、Boc-Asp(OtBu)-OSu、Boc-Asparaginol、Boc-Asp-OBzl、Boc-Asp-OMe、Boc-Asp-OtBu、Boc-Bip(44’)-OH、Boc-Cha-OH、Boc-Chg-OH、Boc-Cit-OH、Boc-Cyclopropylglycine、Boc-Cys(Acm)-OH、Boc-Cys(Acm)-ONp、Boc-Cys(Bzl)-OH、Boc-Cys(Bzl)-OSu、Boc-Cys(Dpm)-OH、Boc-Cys(MMt)-OH、Boc-Cys(Npys)-OH、Boc-Cys(pMeBzl)-OH、Boc-Cys(pMeOBzl)-OH、Boc-Cys(tBu)-OH、Boc-Cys(Trt)-OH、Boc-Cys(Trt)-OH·DCHA、Boc-Cys(Trt)-OSu、Boc-Cysteinol(Bzl)、Boc-Cysteinol(pMeBzl)、Boc-D-1-Nal-OH、Boc-D-2-Nal-OH、Boc-D-2-Pal-OH、Boc-D-3-Pal-OH、Boc-D-4-Pal-OH、Boc-Dab(Boc)-OH·DCHA、Boc-Dab(Fmoc)-OH、Boc-Dab(Z)-OH·DCHA、Boc-Dab-OH、Boc-D-Abu-OH、Boc-D-Abu-OH·DCHA、Boc-D-Ala(33-diphenyl)-OH、Boc-D-Ala-NH2、Boc-D-Alaninol、Boc-D-Ala-OH、Boc-D-Ala-OMe、Boc-D-Ala-ONp、Boc-D-Ala-OSu、Boc-D-Allo-Ile-OH、Boc-D-Allo-Ile-OH·DCHA、Boc-Dap(Boc)-OH·DCHA、Boc-Dap(Fmoc)-OH、Boc-Dap(Z)-OH、Boc-Dap(Z)-OH·DCHA、Boc-Dap-OH、Boc-D-Arg(Mtr)-OH、Boc-D-Arg(Mts)-OH·CHA、Boc-D-Arg(Pbf)-OH、Boc-D-Arg(Tos)-OH、Boc-D-Arg-OH·HCl·H2O、Boc-D-Asn(Trt)-OH、Boc-D-Asn-OH、Boc-D-Asp(OBzl)-OH、Boc-D-Asp(OcHex)-OH、Boc-D-Asp(OMe)-OH、Boc-D-Asp(OtBu)-OH、Boc-D-Asp(OtBu)-OH·DCHA、Boc-D-Asp-OBzl、Boc-D-Asp-OH、Boc-D-Asp-OMe、Boc-D-Asp-OtBu、Boc-D-Cha-OH、Boc-D-Chg-OH、Boc-D-Cys(Acm)-OH、Boc-D-Cys(Dpm)-OH、Boc-D-Cys(pMeBzl)-OH、Boc-D-Cys(pMeOBzl)-OH、Boc-D-Cys(Trt)-OH、Boc-D-Cysteinol(Bzl)、Boc-D-Cysteinol(pMeBzl)、Boc-D-Dap(Fmoc)-OH、Boc-D-Dap-OH、Boc-D-Gln(Trt)-OH、Boc-D-Gln(Xan)-OH、Boc-D-Glu(OBzl)-Osu、Boc-D-Glu(OcHex)-OH、Boc-D-Glu(OMe)-OH、Boc-D-Glu(OMe)-OH·DCHA、Boc-D-Glu(OtBu)-OH、Boc-D-Glu-NH2、Boc-D-Glu-OBzl、Boc-D-Glu-OBzl·DCHA、Boc-D-Gly(Allyl)-OH·DCHA、Boc-D-His(Bom)-OH、Boc-D-His(DNp)-OH·IPA、Boc-D-His(Tos)-OH、Boc-D-His(Trt)-OH、Boc-D-His-OH、Boc-D-HoPhe-OH、Boc-D-HoPro-OH、Boc-D-Hyp-OMe、Boc-D-Ile-OH、Boc-DL-Abu-OH、Boc-DL-Ala-OH、Boc-DL-Asp(OBzl)-OH、Boc-D-Leucinol、Boc-D-Leu-OH·H2O、Boc-DL-Leu-OH·H2O、Boc-DL-Met-OH、Boc-DL-Phe(4-NO2)-OH、Boc-DL-Phenylalaninol、Boc-DL-Phenylglycinol、Boc-DL-Phe-OH、Boc-DL-Phg-OH、Boc-DL-Prolinol、Boc-DL-Pro-OH、Boc-DL-Ser(Bzl)-OH、Boc-DL-Tle-OH、Boc-DL-Tyr-OH、Boc-D-Lys(2-Cl-Z)-OH、Boc-D-Lys(Boc)-OH、Boc-D-Lys(Boc)-OH·DCHA、Boc-D-Lys(Boc)-ONp、Boc-D-Lys(Boc)-OSu、Boc-D-Lys(Fmoc)-OH、Boc-D-Lys(Tfa)-OH、Boc-D-Lys(Z)-OH、Boc-D-Lysinol(Z)、Boc-D-Lys-OH、Boc-DL-β-HoPhe-OH、Boc-D-Methioninol、Boc-D-Met-OH、Boc-D-N-Me-Ala-OH、Boc-D-N-Me-Phe-OH·DCHA、Boc-D-N-Me-Phg-OH、Boc-D-N-Me-Tyr(Bzl)-OH、Boc-D-Nva-OH·DCHA、Boc-Dopa-OH、Boc-D-Orn(Me2)-OH、Boc-D-Orn(Z)-OH、Boc-D-Orn(Z)-OSu、Boc-D-Orn-OH、Boc-D-Pen(pMeBzl)-OH·DCHA、Boc-D-Phe(2-Br)-OH、Boc-D-Phe(3,4-DiF)-OH、Boc-D-Phe(34-Cl2)-OH、Boc-D-Phe(3-CF3)-OH、Boc-D-Phe(3-Cl)-OH、Boc-D-Phe(4-Br)-OH、Boc-D-Phe(4-Cl)-OH、Boc-D-Phe(4-CN)-OH、Boc-D-Phe(4-F)-OH、Boc-D-Phe(4-I)-OH、Boc-D-Phe(4-Me)-OH、Boc-D-Phe(4-NH2)-OH、Boc-D-Phe(4-NO2)-OH、Boc-D-Phenylalaninol、Boc-D-Phenylglycinol、Boc-D-Phe-OH、Boc-D-Phe-ONp、Boc-D-Phg-OH、Boc-D-Pra-OH、Boc-D-Prolinol、Boc-D-Pro-OH、Boc-D-Pro-OSu、Boc-D-Ser(Bzl)-OH、Boc-D-Ser(Me)-OH、Boc-D-Ser(Me)-OH·DCHA、Boc-D-Ser(tBu)-OH、Boc-D-Ser(tBu)-OH·DCHA、Boc-D-Serinol(Bzl)、 Boc-D-Ser-OBzl、Boc-D-Ser-OH、Boc-D-Ser-OMe、Boc-D-Thr(Bzl)-OH、Boc-D-Thr(Me)-OH、Boc-D-Thr(tBu)-OH、Boc-D-Threoninol(Bzl)、Boc-D-Thr-OH、Boc-D-Thz-OH、Boc-D-Trp(Boc)-OH、Boc-D-Trp(For)-OH、Boc-D-Trp-OH、Boc-D-Tryptophanol、Boc-D-Tyr(2-Br-Z)-OH、Boc-D-Tyr(3-I)-OH、Boc-D-Tyr(All)-OH、Boc-D-Tyr(All)-OH·DCHA、Boc-D-Tyr(Bzl)-OH、Boc-D-Tyr(Et)-OH、Boc-D-Tyr(Me)-OH、Boc-D-Tyr(tBu)-OH、Boc-D-Tyr-OH、Boc-D-Tyr-OMe、Boc-D-Valinol、Boc-D-Val-OH、Boc-Gln(Trt)-OH、Boc-Gln(Xan)-OH、Boc-Gln-OH、Boc-Gln-ONp、Boc-Glu(OBzl)-OH、Boc-Glu(OBzl)-OMe、Boc-Glu(OcHex)-OH、Boc-Glu(OcHex)-OH·DCHA、Boc-Glu(OFm)-OH、Boc-Glu(OMe)-OH、Boc-Glu(OMe)-OMe、Boc-Glu(OSu)-OBzl、Boc-Glu(OSu)-OSu、Boc-Glu(OtBu)-OH、Boc-Glu(OtBu)-ONp、Boc-Glu(OtBu)-OSu、Boc-Glu-NH2、Boc-Glu-OBzl·DCHA、Boc-Glu-OH、Boc-Glu-OMe、Boc-Glu-OtBu、Boc-Glutaminol、Boc-Glutamol(OBzl)、Boc-Glycinol、Boc-Gly-Gly-Gly-OH、Boc-Gly-Leu-OH、Boc-Gly-N(OMe)Me、Boc-Gly-NH2、Boc-Gly-OEt、Boc-Gly-OH、Boc-Gly-OMe、Boc-Gly-OSu、Boc-Gly-OtBu、Boc-Gly-Pro-OH、Boc-His(1-Me)-OH、Boc-His(3-Bom)-OMe·HCl、Boc-His(Boc)-OH、Boc-His(Boc)-OH·Benzene、Boc-His(Boc)-OH·DCHA、Boc-His(Boc)-OH·DCHA、Boc-His(Bom)-OH、Boc-His(Dnp)-OH、Boc-His(Dnp)-OH·IPA、Boc-His(Tos)-OH、Boc-His(Trt)-OH、Boc-His(Z)-OH、Boc-His-Gly-OH、Boc-His-OH、Boc-Histidinol(Tos)、Boc-HoArg(NO2)-OH、Boc-HoPhe-OH、Boc-HoPro-OH、Boc-HoSer(Bzl)-OH、Boc-HoTyr-OH、Boc-Hyp(Bzl)-OH·DCHA、Boc-Hyp-OEt、Boc-Hyp-OH、Boc-Hyp-OL、Boc-Hyp-OMe、Boc-Ida-OH、Boc-Ile-OH·1 / 2H2O、Boc-Ile-OSu、Boc-Inp-OH、Boc-Inp-OSu、Boc-isoleucinol、Boc-Leucinol、Boc-Leu-Gly-OH、Boc-Leu-OH·H2O、Boc-Leu-OMe、Boc-Leu-OSu、Boc-L-M-Tyrosine、Boc-Lys(2-Cl-Z)-OH、Boc-Lys(Ac)-OH、Boc-Lys(Ac)-pNA、Boc-Lys(Boc)-OH、Boc-Lys(Boc)-OH·DCHA、Boc-Lys(Boc)-OMe、Boc-Lys(Boc)-ONp、Boc-Lys(Boc)-OSu、Boc-Lys(Boc)-Pro-OH、Boc-Lys(Fmoc)-OH、Boc-Lys(Fmoc)-OMe、Boc-Lys(For)-OH、Boc-Lys(Tfa)-OH、Boc-Lys(Z)-OH、Boc-Lys(Z)-OSu、Boc-Lys(Z)-pNA、Boc-Lysinol(2-Cl-Z)、Boc-Lysinol(Z)、Boc-Lys-OH、Boc-Lys-OMe·HCl、Boc-Lys-OSu、Boc-Lys-OtBu、Boc-Met(O)-OH、Boc-Met(O2)-OH、Boc-Methioninol、Boc-Met-OH(oil)、Boc-Met-OH(powder)、Boc-Met-OSu、Boc-Nip-OH、Boc-Nle-OH、Boc-Nle-OH·DCHA、Boc-N-Me-Ala-OH、Boc-N-Me-Arg(Mtr)-OH、Boc-N-Me-Glu(OBzl)-OH、Boc-N-Me-Nle-OH、Boc-N-Me-Phe-OH·DCHA、Boc-N-Me-Phg-OH、Boc-N-Me-Ser(tBu)-OH、Boc-N-Me-Ser-OH、Boc-N-Me-Ser-OH·DCHA、Boc-N-Me-Tyr(Bzl)-OH、Boc-N-Me-Tyr-OH·DCHA、Boc-N-Me-Val-OH、Boc-N-Me-Val-OH·DCHA、Boc-Norvalinol、Boc-Nva-OH·DCHA、Boc-Nva-OSu、Boc-ON、Boc-Orn(2-Cl-Z)-OH、Boc-Orn(Alloc)-OH·DCHA、Boc-Orn(Fmoc)-OH、Boc-Orn(Z)-OH、Boc-Orn(Z)-OSu、Boc-Orn-OH、Boc-Pen(pMeBzl)-OH、Boc-Phe(2-Br)-OH、Boc-Phe(2-F)-OH、Boc-Phe(2-Me)-OH、Boc-Phe(3,4-DiCl)-OH、Boc-Phe(3,4-DiF)-OH、Boc-Phe(345-TriF)-OH、Boc-Phe(3-F)-OH、Boc-Phe(4-Br)-OH、Boc-Phe(4-Cl)-OH、Boc-Phe(4-F)-OH、Boc-Phe(4-I)-OH、Boc-Phe(4-I)-OMe、Boc-Phe(4-NH2)-OH、Boc-Phe(4-NH2)-OMe、Boc-Phe(4-NHFmoc)-OH、Boc-Phe(4-NHZ)-OH、Boc-Phe(4-NO2)-OH、Boc-Phe-Gly-OMe、Boc-Phe-Leu-OH、Boc-Phenylalaninol、Boc-Phenylglycinol、Boc-Phe-OH、Boc-Phe-OMe、Boc-Phe-ONp、Boc-Phe-OSu、Boc-Phe-Phe-OH、Boc-Phg-OH、Boc-Pra-OH、Boc-Pro-N(OMe)Me、Boc-Pro-NHEt、Boc-Pro-OH、Boc-Pro-OMe、Boc-Pro-Phe-OH、Boc-Pyr-OH、Boc-Pyr-OtBu、Boc-Sar-OH、Boc-Sar-OSu、Boc-Ser(Ac)-OH·DCHA、Boc-Ser(Bzl)-OH、Boc-Ser(Fmoc-Leu)-OH、Boc-Ser(Fmoc-Ser(tBu))-OH、Boc-Ser(Me)-OH、Boc-Ser(Me)-OH·DCHA、Boc-Ser(PO3Bzl2)-OH、Boc-Ser(tBu)-OH、Boc-Ser(tBu)-OH·DCHA、Boc-Ser(Tos)-OMe、Boc-Ser(Trt)-OH、Boc-Serinol(Bzl)、Boc-Ser-OBzl、Boc-Ser-OEt、Boc-Ser-OH、Boc-Ser-OH·DCHA、Boc-Ser-OMe、Boc-Tea-OH·DCHA、Boc-Thr(Bzl)-OH、Boc-Thr(Fmoc-Val)-OH、Boc-Thr(Me)-OH、Boc-Thr(tBu)-OH、Boc-Threoninol(Bzl)、Boc-Thr-OBzl、Boc-Thr-OH、Boc-Thr-OMe、Boc-Thr-OSu、Boc-Thz-OH、Boc-Tic-OH、Boc-Tle-OH、Boc-Tos-Ser-OMe、Boc-Trp(Boc)-OH、Boc-Trp(For)-OH、Boc-Trp(Hoc)-OH、Boc-Trp-OBzl、Boc-Trp-OH、Boc-Trp-OMe、Boc-Trp-OSu、Boc-Trp-Phe-OMe、Boc-Tryptophanol、Boc-Tyr(2-Br-Z)-OH、Boc-Tyr(2-Cl-Z)-OH、Boc-Tyr(3-Cl)-OH·DCHA、Boc-Tyr(Bzl)-OH、Boc-Tyr(Bzl)-OSu、Boc-Tyr(Me)-OH、Boc-Tyr(Me)-OMe、Boc-Tyr(tBu)-OH、Boc-Tyr-OEt、Boc-Tyr-OH、Boc-Tyr-OMe、Boc-Tyrosinol、Boc-Tyr-OSu、Boc-Tyr-OtBu、Boc-Val-Ala-OH、Boc-Val-Gly-OH、Boc-Valinol、Boc-Val-NH2、Boc-Val-OH、Boc-Val-OMe、Boc-Val-OSu、Boc-β-Ala-NH2、Boc-β-Ala-OH、Boc-β-Ala-OSu、Boc-β-HoAla-OH、Boc-β-HoArg(Tos)-OH、Boc-β-HoAsn-OH、Boc-β-HoAsp(OBzl)-OH、Boc-β-HoGln-OH、Boc-β-HoGlu(OBzl)-OH、Boc-β-HoIle-OH、Boc-β-HoPhe-OH、Boc-β-HoPro-OH、Boc-β-HoSer(Bzl)-OH、Boc-β-HoVal-OH、Boc-β-Iodo-Ala-OMe、Boc-ε-Acp-OH、Bz-Ala-OH、Bz-Arg-NH2·HCl·H2O、Bz-Arg-OEt·HCl、Bz-Arg-OH、Bz-Arg-OMe·HCl、Bz-Arg-pNA·HCl、Bz-DL-Arg-pNA·HCl、Bz-DL-Leu-OH、Bz-D-Phe-OH、Bz-Gln-OH、Bz-Glu-OH、Bzl-Gly-OH·HCl、Bzl-Hyp-OMe、Bzl-Pro-OH、Bz-Lys-OH、Bz-Nle-OH、Bz-Orn-OH、Bz-Phe-OH、Bz-Pro-OMe、Bz-Tyr-OEt、Bz-Tyr-pNA、D-Alaninol、D-Biotin、D-Biotin-EDA、Dde-Lys(Dde)-OH、Dde-Lys(Fmoc)-OH、DEPBT、Di-Bzl-Gly-OEt、D-Leucinol、DL-Methioninol、DL-m-Tyrosine、DL-Penylalaninol、DL-Phenylglycinol、DL-Prolinol、DL-Valinol、D-Methioninol、D-Penylalaninol、D-Phenylglycinol、D-Prolinol(oil)、D-Threoninol、D-Tryptophanol、D-Tyrosinol、D-Valinol、Fmoc-Argininol(Pbf)、Fmoc-β-(2-thienyl)-D-Alanine、Fmoc-(Dmb)Ala-OH、Fmoc-(Dmb)Gly-OH、Fmoc-(Fmoc-Hmb)-Ala-OH、Fmoc-(Fmoc-Hmb)-Lys(Boc)-OH、Fmoc-(Fmoc-Hmb)-Val-OH、Fmoc-(N-ethyl)-L-Glutamine、Fmoc-13-diaminopropane hydrochloride、Fmoc-1-Nal-OH、Fmoc-2-Abz-OH、Fmoc-2-Nal-OH、Fmoc-2-Pal-OH、Fmoc-3-(4-thiazolyl)-Alanine、Fmoc-3-Abz-OH、Fmoc-3-Pal-OH、Fmoc-4-Abz-OH、Fmoc-4-Amb-OH、Fmoc-4-Amc-OH、Fmoc-4-Pal-OH、Fmoc-5-Ava-、 OH、Fmoc-7-Ahp-OH、Fmoc-8-Aoc-OH、Fmoc-Abu-OH、Fmoc-Aib-OH、Fmoc-Ala-Cl、Fmoc-Alaninol、Fmoc-Ala-OH、Fmoc-Ala-OMe、Fmoc-Ala-OPfp、Fmoc-Ala-OSu、Fmoc-Ala-Ser[Psi(MeMe)Pro]-OH、Fmoc-Ala-Thr[Psi(MeMe)Pro]-OH、Fmoc-Allo-Thr(tBu)-OH、Fmoc-Aph(Hor)-OH、Fmoc-Arg(Alloc)2-OH、Fmoc-Arg(Boc)2-OH、Fmoc-Arg(Me)2-OH·HCl、Fmoc-Arg(MePbf)-OH、Fmoc-Arg(Mtr)-OH、Fmoc-Arg(Mtr)-Opfp、Fmoc-Arg(Mts)-OH、Fmoc-Arg(NO2)-OH、Fmoc-Arg(Pbf)-Gly-OH、Fmoc-Arg(Pbf)-NH2、Fmoc-Arg(Pbf)-OH、Fmoc-Arg(Pbf)-OPfp、Fmoc-Arg(Tos)-OH、Fmoc-Argininol(Tos)、Fmoc-Arg-OH、Fmoc-Arg-OH·HCl、Fmoc-Asn(Trt)-OH、Fmoc-Asn(Trt)-Opfp、Fmoc-Asn(Trt)-Ser[Psi(MeMe)Pro]-OH、Fmoc-Asn(Trt)-Thr[Psi(MeMe)Pro]-OH、Fmoc-Asn-OH、Fmoc-Asn-Opfp、Fmoc-Asp(Edans)-OH、Fmoc-Asp(OAll)-OH、Fmoc-Asp(OBzl)-OH、Fmoc-Asp(OcHex)-OH、Fmoc-Asp(ODMAB)-OH、Fmoc-Asp(OMe)-OH、Fmoc-Asp(OMpe)-OH、Fmoc-Asp(OtBu)-Glu(OtBu)-NH2、Fmoc-Asp(OtBu)-N(Hmb)-Gly-OH、Fmoc-Asp(OtBu)-OH、Fmoc-Asp(OtBu)-OPfp、Fmoc-Asp(OtBu)-OSu、Fmoc-Asp(OtBu)-Ser[Psi(MeMe)Pro]-OH、Fmoc-Asp(OtBu)-Thr[Psi(MeMe)Pro]-OH、Fmoc-Asparaginol、Fmoc-Asparaginol(Trt)、Fmoc-Aspartimol(OtBu)、Fmoc-Asp-OAll、Fmoc-Asp-OBzl、Fmoc-Asp-OFm、Fmoc-Asp-OH、Fmoc-Asp-OMe、Fmoc-Asp-OtBu、Fmoc-Bip(44’)-OH、Fmoc-Bpa-OH、Fmoc-Cha-OH、Fmoc-Chg-OH、Fmoc-Cit-OH、Fmoc-Cl、Fmoc-Cpg-OH、Fmoc-Cycloheptyl-Ala-OH、Fmoc-Cyclopropylglycine、Fmoc-Cys(Ac)-OH、Fmoc-Cys(Acm)-OH、Fmoc-Cys(Acm)-OPfp、Fmoc-Cys(Bzl)-OH、Fmoc-Cys(CAM)-OH、Fmoc-Cys(Dpm)-OH、Fmoc-Cys(Et)-OH、Fmoc-Cys(Me)-OH、Fmoc-Cys(MMt)-OH、Fmoc-Cys(Mtt)-OH、Fmoc-Cys(Pam)2-OH(R)、Fmoc-Cys(Pam)2-OH(S)、Fmoc-Cys(pMeBzl)-OH、Fmoc-Cys(pMeOBzl)-OH、Fmoc-Cys(SO3H)-OH、Fmoc-Cys(StBu)-OH、Fmoc-Cys(tBu)-OH、Fmoc-Cys(tert-butoxycarnylpropyl)-OH、Fmoc-Cys(Trt)-NH2、Fmoc-Cys(Trt)-OH、Fmoc-Cys(Trt)-Opfp、Fmoc-Cys(Xan)-OH、Fmoc-Cysteinol(Acm)、Fmoc-Cysteinol(Trt)、Fmoc-D-1-Nal-OH、Fmoc-D-2-Nal-OH、Fmoc-D-3-Pal-OH、Fmoc-D-4-Pal-OH、Fmoc-Dab(Alloc)-OH、Fmoc-Dab(Boc)-OH、Fmoc-Dab(Dde)-OH、Fmoc-Dab(Fmoc)-OH、Fmoc-Dab(ivDde)-OH、Fmoc-Dab(Mtt)-OH、Fmoc-Dab(Z)-OH、Fmoc-Dab-OH、Fmoc-D-Abu-OH、Fmoc-D-Ala-NH2、Fmoc-D-Alaninol、Fmoc-D-Ala-OH、Fmoc-D-Ala-OPfp、Fmoc-D-Allo-Ile-OH、Fmoc-D-Allo-Ile-OPfp、Fmoc-D-Allo-Thr(tBu)-OH、Fmoc-Dap(Alloc)-OH、Fmoc-Dap(Boc)-OH、Fmoc-Dap(Dde)-OH、Fmoc-Dap(Dnp)-OH、Fmoc-Dap(Mtt)-OH、Fmoc-Dap(Z)-OH、Fmoc-D-Aph(Cbm)-OH、Fmoc-D-Aph(L-Hor)-OH、Fmoc-D-Aph(tBuCbm)-OH、Fmoc-Dap-OH、Fmoc-D-Arg(Me)2-OH·HCl、Fmoc-D-Arg(Mtr)-OH、Fmoc-D-Arg(NO2)-OH、Fmoc-D-Arg(Pbf)-OH、Fmoc-D-Arg(Tos)-OH、Fmoc-D-Arg-OH、Fmoc-D-Arg-OH·HCl、Fmoc-D-Asn(Trt)-OH、Fmoc-D-Asn-OH、Fmoc-D-Asp(OAll)-OH、Fmoc-D-Asp(OBzl)-OH、Fmoc-D-Asp(OtBu)-OH、Fmoc-D-Asp(OtBu)-Opfp、Fmoc-D-Aspartimol(OtBu)、Fmoc-D-Asp-OAll、Fmoc-D-Asp-OBzl、Fmoc-D-Asp-OH、Fmoc-D-Asp-OMe、Fmoc-D-Asp-OtBu、Fmoc-D-Bip(44’)-OH、Fmoc-D-Bpa-OH、Fmoc-D-Cha-OH、Fmoc-D-Chg-OH、Fmoc-D-Cit-OH、Fmoc-D-Cys(Acm)-OH、Fmoc-D-Cys(Dpm)-OH、Fmoc-D-Cys(Mmt)-OH、Fmoc-D-Cys(tBu)-OH、Fmoc-D-Cys(Trt)-OH、Fmoc-D-Cys(Trt)-OPfp、Fmoc-D-Dab(Boc)-OH、Fmoc-D-Dab(Dde)-OH、Fmoc-D-Dab(Z)-OH、Fmoc-D-Dab-OH、Fmoc-D-Dap(Boc)-OH、Fmoc-D-Dap-OH、Fmoc-Deg-OH、Fmoc-D-Gln(Trt)-OH、Fmoc-D-Gln-OH、Fmoc-D-Gln-OPfp、Fmoc-D-Glu(OBzl)-OH、Fmoc-D-Glu(OMe)-OH、Fmoc-D-Glu(OtBu)-OH、Fmoc-D-Glu(OtBu)-OPfp、Fmoc-D-Glu-OAll、Fmoc-D-Glu-OH、Fmoc-D-Glu-OtBu、Fmoc-D-His(Boc)-OH·CHA、Fmoc-D-His(Fmoc)-OH、Fmoc-D-His(Trt)-OH、Fmoc-D-His-OH、Fmoc-D-HoArg-OH、Fmoc-D-HoArg-OH·HCl、Fmoc-D-HoCit-OH、Fmoc-D-HoCys(Trt)-OH、Fmoc-D-HoPhe-OH、Fmoc-D-HoPro-OH、Fmoc-D-Ile-OH、Fmoc-D-isoGln-OH、Fmoc-DL-Ala-OH、Fmoc-DL-Asp(OtBu)-OH、Fmoc-D-Leu-D-Ser(psi(MeMe)-Pro)-OH、Fmoc-D-Leu-OH、Fmoc-D-Leu-OPfp、Fmoc-DL-Gly(allyl)-OH、Fmoc-DL-Phe(4-NO2)-OH、Fmoc-DL-Phe-OH、Fmoc-DL-Pra-OH、Fmoc-DL-Tyr(Me)-OH、Fmoc-D-Lys(2-Cl-Z)-OH、Fmoc-D-Lys(Ac)-OH、Fmoc-D-Lys(Alloc)-OH、Fmoc-D-Lys(Boc)-OH、Fmoc-D-Lys(Boc)-OPfp、Fmoc-D-Lys(Dde)-OH、Fmoc-D-Lys(Fmoc)-OH、Fmoc-D-Lys(Mtt)-OH、Fmoc-D-Lys(Z)-OH、Fmoc-D-Lys-OH·HCl、Fmoc-D-Met(O)-OH、Fmoc-D-Met-OH、Fmoc-D-Met-OPfp、Fmoc-D-Nle-OH、Fmoc-D-N-Me-Leu-OH、Fmoc-D-N-Me-Phe-OH、Fmoc-D-N-Me-Val-OH、Fmoc-D-Nva-OH、Fmoc-Dopa(acetonide)-OH、Fmoc-D-Orn(Alloc)-OH、Fmoc-D-Orn(Boc)-OH、Fmoc-D-Pen(Trt)-OH、Fmoc-D-Phe(2-Cl)-OH、Fmoc-D-Phe(3,4-DiCl)-OH、Fmoc-D-Phe(3-Cl)-OH、Fmoc-D-Phe(4-Br)-OH、Fmoc-D-Phe(4-Cl)-OH、Fmoc-D-Phe(4-CN)-OH、Fmoc-D-Phe(4-I)-OH、Fmoc-D-Phe(4-Me)-OH、Fmoc-D-Phe(4-NH2)-OH、Fmoc-D-Phe(4-NHBoc)-OH、Fmoc-D-Phe(4-NO2)-OH、Fmoc-D-Phe(F5)-OH、Fmoc-D-Phe-OH、Fmoc-D-Phe-OPfp、Fmoc-D-Phg(4-NO2)-OH、Fmoc-D-Phg-OH、Fmoc-D-Pra-OH、Fmoc-D-Pro-OH、Fmoc-D-Pro-OPfp、Fmoc-D-Ser(Ac)-OH、Fmoc-D-Ser(Bzl)-OH、Fmoc-D-Ser(HPO3Bzl)-OH、Fmoc-D-Ser(Me)-OH、Fmoc-D-Ser(tBu)-OH、Fmoc-D-Ser(tBu)-OPfp、Fmoc-D-Ser(Trt)-OH、Fmoc-D-Ser-OH、Fmoc-D-Ser-OMe、Fmoc-D-Thr(Ac)-OH、Fmoc-D-Thr(tBu)-OH、Fmoc-D-Thr(tBu)-OPfp、Fmoc-D-Threoninol、Fmoc-D-Threoninol(tBu)、Fmoc-D-Thr-OH·H2O、Fmoc-D-Thz-OH、Fmoc-D-Tic-OH、Fmoc-D-Tle-OH、Fmoc-D-trans-Hyp(tBu)-OH、Fmoc-D-Trp(Boc)-OH、Fmoc-D-Trp-OH、Fmoc-D-Trp-OPfp、Fmoc-D-Tryptophanol、Fmoc-D-Tyr(3-Cl)-OH、Fmoc-D-Tyr(3-I)-OH、Fmoc-D-Tyr(3-NO2)-OH、Fmoc-D-Tyr(4-Et)-OH、Fmoc-D-Tyr(Ac)-OH、Fmoc-D-Tyr(Bzl)-OH、Fmoc-D-Tyr(HPO3Bzl)-OH、Fmoc-D-Tyr(Me)-OH、Fmoc-D-Tyr(tBu)-OH、Fmoc-D-Tyr(tBu)-OPfp、Fmoc-D-Tyr-OH、Fmoc-D-Val-OH、Fmoc-D-Val-OPfp、Fmoc-Gln(Trt)-OH、Fmoc-Gln(Trt)-OPfp、Fmoc-Gln(Trt)-Ser[Psi(MeMe)Pro]-OH、Fmoc-Gln(Trt)-Thr[Psi(MeMe)Pro]-OH、Fmoc-Gln-OH、Fmoc-Gln-OPfp、Fmoc-Glu(Alloc)-OH、Fmoc-Glu(Edans)-OH、Fmoc-Glu(OAll)-OH、Fmoc-Glu(OBzl)-OBzl、Fmoc-Glu(OBzl)-OH、Fmoc-Glu(OcHex)-OH、Fmoc-Glu(O、 dmab)-OH、Fmoc-Glu(OMe)-OH、Fmoc-Glu(OSu)-OSu、Fmoc-Glu(OtBu)-Glu(OtBu)-NH2、Fmoc-Glu(OtBu)-Gly-OH、Fmoc-Glu(OtBu)-OH、Fmoc-Glu(OtBu)-OPfp、Fmoc-Glu(OtBu)-Ser[Psi(MeMe)Pro]-OH、Fmoc-Glu(OtBu)-Thr[Psi(MeMe)Pro]-OH、Fmoc-Glu-OAll、Fmoc-Glu-OBzl、Fmoc-Glu-OH、Fmoc-Glu-OMe、Fmoc-Glu-OtBu、Fmoc-Glutaminol、Fmoc-Glutamol(OtBu)、Fmoc-Gly(allyl)-OH、Fmoc-Glycinol、Fmoc-Gly-Cl、Fmoc-Gly-D-Ser(psi(MeMe)-Pro)-OH、Fmoc-Gly-Gly-Gly-OH、Fmoc-Gly-Gly-OH、Fmoc-Gly-HMBA-MBHA-Resin、Fmoc-Gly-OH、Fmoc-Gly-OPfp、Fmoc-Gly-OSu、Fmoc-Gly-Ser(Psi(MeMe)Pro)-OH、Fmoc-Gly-Thr[Psi(MeMe)Pro]-OH、Fmoc-His(Boc)-OH·CHA、Fmoc-His(Boc)-OH·DCHA、Fmoc-His(Bzl)-OH、Fmoc-His(Clt)-OH、Fmoc-His(DNP)-OH、Fmoc-His(Fmoc)-OH、Fmoc-His(MMt)-OH、Fmoc-His(Mtt)-OH、Fmoc-His(Trt)-OH、Fmoc-His(Trt)-OPfp、Fmoc-His(Z)-OH、Fmoc-HoArg(Pbf)-OH、Fmoc-HoArg-OH、Fmoc-HoArg-OH·HCl、Fmoc-HoCit-OH、Fmoc-HoCys(Trt)-OH、Fmoc-HoLeu-OH、Fmoc-HomoArg(Me)2-OH·HCl、Fmoc-HoPhe-OH、Fmoc-HoPro-OH、Fmoc-HoSer(Trt)-OH、Fmoc-HoTyr-OH·DCHA、Fmoc-Hyp(Bom)-OH、Fmoc-Hyp(Bzl)-OH、Fmoc-Hyp(tBu)-OH、Fmoc-Hyp-OBzl、Fmoc-Hyp-OH、Fmoc-Hyp-OMe、Fmoc-Ida-OH、Fmoc-Ile-OH、Fmoc-Ile-OPfp、Fmoc-Ile-Pro-OH、Fmoc-Ile-Ser[Psi(MeMe)Pro]-OH、Fmoc-Ile-Thr[Psi(MeMe)Pro]-OH、Fmoc-Inp-OH、Fmoc-isoGln-OH、Fmoc-isoleucinol、Fmoc-Leucinol、Fmoc-Leu-OH、Fmoc-Leu-OPfp、Fmoc-Leu-OSu、Fmoc-Leu-Ser[Psi(MeMe)Pro]-OH、Fmoc-Leu-Thr[Psi(MeMe)Pro]-OH、Fmoc-Lys(2-Cl-Z)-OH、Fmoc-Lys(Ac)-OH、Fmoc-Lys(Alloc)-OH、Fmoc-Lys(Biotin)-OH、Fmoc-Lys(Boc)-OH、Fmoc-Lys(Boc)-OPfp、Fmoc-Lys(Boc)-OSu、Fmoc-Lys(Boc)-Ser[Psi(MeMe)Pro]-OH、Fmoc-Lys(Boc)-Thr[Psi(MeMe)Pro]-OH、Fmoc-Lys(BocMe)-OH、Fmoc-Lys(Bz)-OH、Fmoc-Lys(Caproyl)-OH、Fmoc-Lys(Dabcyl)-OH、Fmoc-Lys(Dansyl)-OH、Fmoc-Lys(Dde)-OH、Fmoc-Lys(Dnp)-OH、Fmoc-Lys(Fmoc)-OH、Fmoc-Lys(Fmoc)-OPfp、Fmoc-Lys(For)-OH、Fmoc-Lys(ipr)-OH、Fmoc-Lys(iprBoc)-OH、Fmoc-Lys(iprBoc)-OH·DCHA、Fmoc-Lys(ivDde)-OH、Fmoc-Lys(Me)2-OH·HCl、Fmoc-Lys(Me)3-OH、Fmoc-Lys(Mtt)-OH、Fmoc-Lys(Nic)-OH、Fmoc-Lys(Palmitoyl)-OH、Fmoc-Lys(Tfa)-OH、Fmoc-Lys(Trt)-OH、Fmoc-Lys(Z)-OH、Fmoc-Lys[Boc-Cys(Trt)]-OH、Fmoc-Lysinol(Boc)、Fmoc-Lys-OAll·HCl、Fmoc-Lys-OH、Fmoc-Lys-OH·HCl、Fmoc-Lys-OMe·HCl、Fmoc-Met(O)-OH、Fmoc-Met(O2)-OH、Fmoc-Met-OH、Fmoc-Met-OPfp、Fmoc-N-(2-Boc-aminoethyl)-Gly-OH、Fmoc-N(Hmb)-Gly-OH、Fmoc-Nip-OH、Fmoc-Nle-OH、Fmoc-N-Me-Ala-OH、Fmoc-N-Me-Arg(Mtr)-OH、Fmoc-N-Me-Asp(OtBu)-OH、Fmoc-N-Me-Glu(OtBu)-OH、Fmoc-N-Me-Ile-OH、Fmoc-N-Me-Leu-OH、Fmoc-N-Me-Lys(Boc)-OH、Fmoc-N-Me-Met-OH、Fmoc-N-Me-Nle-OH、Fmoc-N-Me-Nva-OH、Fmoc-N-Me-Phe-OH、Fmoc-N-Me-Ser(Me)-OH、Fmoc-N-Me-Ser(tBu)-OH、Fmoc-N-Me-Thr(Bzl)-OH、Fmoc-N-Me-Thr(tBu)-OH、Fmoc-N-Me-Thr-OH、Fmoc-N-Me-Tyr(tBu)-OH、Fmoc-N-Me-Val-OH、Fmoc-Nva-OH、Fmoc-Oic-OH、Fmoc-O-Phospho-Tyrosine、Fmoc-Orn(2-Cl-Z)-OH、Fmoc-Orn(Alloc)-OH、Fmoc-Orn(Boc)-OH、Fmoc-Orn(Dde)-OH、Fmoc-Orn(Fmoc)-OH、Fmoc-Orn(ivDde)-OH、Fmoc-Orn(Mtt)-OH、Fmoc-Orn(Trt)-OH、Fmoc-Orn(Z)-OH、Fmoc-Orn-OH·HCl、Fmoc-OSu、Fmoc-Pen(Trt)-OH、Fmoc-Phe(2,6-DiF)-OH、Fmoc-Phe(2-Br)-OH、Fmoc-Phe(2-Cl)-OH、Fmoc-Phe(2-F)-OH、Fmoc-Phe(3,4-DiF)-OH、Fmoc-Phe(3,5-DiF)-OH、Fmoc-Phe(3-Br)-OH、Fmoc-Phe(3-Cl)-OH、Fmoc-Phe(3-F)-OH、Fmoc-Phe(4-Ac)-OH、Fmoc-Phe(4-Br)-OH、Fmoc-Phe(4-CF3)-OH、Fmoc-Phe(4-Cl)-OH、Fmoc-Phe(4-CN)-OH、Fmoc-Phe(4-F)-OH、Fmoc-Phe(4-I)-OH、Fmoc-Phe(4-Me)-OH、Fmoc-Phe(4-NH2)-OH、Fmoc-Phe(4-NO2)-OH、Fmoc-Phe(F5)-OH、Fmoc-Phenylalaninol、Fmoc-Phe-OH、Fmoc-Phe-OMe、Fmoc-Phe-OPfp、Fmoc-Phe-Ser[Psi(MeMe)Pro]-OH、Fmoc-Phe-Thr[Psi(MeMe)Pro]-OH、Fmoc-Phg-OH、Fmoc-Pra-OH、Fmoc-Pro-Leu-Gly-OH、Fmoc-Prolinol、Fmoc-Pro-OH、Fmoc-Pro-OPfp、Fmoc-Pro-OSu、Fmoc-Sar-OH、Fmoc-Sec(mob)-OH、Fmoc-Ser(Ac)-OH、Fmoc-Ser(Bzl)-OH、Fmoc-Ser(Et)-OH、Fmoc-Ser(HPO3Bzl)-OH、Fmoc-Ser(Me)-OH、Fmoc-Ser(TBDMS)-OH、Fmoc-Ser(tBu)-OH、Fmoc-Ser(tBu)-OPfp、Fmoc-Ser(tBu)-Ser[Psi(MeMe)Pro]-OH、Fmoc-Ser(tBu)-Thr[Psi(MeMe)Pro]-OH、Fmoc-Ser(Trt)-OH、Fmoc-Serinol、Fmoc-Serinol(tBu)、Fmoc-Ser-OBzl、Fmoc-Ser-OH、Fmoc-Ser-OMe、Fmoc-Ser-OPAC、Fmoc-Thr(Ac)-OH、Fmoc-Thr(Bzl)-OH、Fmoc-Thr(Et)-OH、Fmoc-Thr(HPO3Bzl)-OH、Fmoc-Thr(Me)-OH、Fmoc-Thr(SO3Na)-OH、Fmoc-Thr(TBDMS)-OH、Fmoc-Thr(tBu)-OH、Fmoc-Thr(tBu)-OPfp、Fmoc-Thr(tBu)-Ser[Psi(MeMe)Pro]-OH、Fmoc-Thr(tBu)-Thr(Psi(MeMe)pro)-OH、Fmoc-Thr(Trt)-OH、Fmoc-Threoninol、Fmoc-Threoninol(tBu)DHP、Fmoc-Thr-OBzl、Fmoc-Thr-OH、Fmoc-Thr-OMe、Fmoc-Thr-OPAC、Fmoc-Thz-OH、Fmoc-Tic-OH、Fmoc-Tle-OH、Fmoc-Trp(5-OH)-OH、Fmoc-Trp(Boc)-OH、Fmoc-Trp(Boc)-Ser[Psi(MeMe)Pro]-OH、Fmoc-Trp(Boc)-Thr[Psi(MeMe)Pro]-OH、Fmoc-Trp-OH、Fmoc-Trp-OPfp、Fmoc-Trp-OSu、Fmoc-Tryptophanol、Fmoc-Tyr(2-Br-Z)-OH、Fmoc-Tyr(3,5-DiI)-OH、Fmoc-Tyr(3-Cl)-OH、Fmoc-Tyr(3-I)-OH、Fmoc-Tyr(3-NO2)-OH、Fmoc-Tyr(Ac)-OH、Fmoc-Tyr(Bzl)-OH、Fmoc-Tyr(HPO3Bzl)-OH、Fmoc-Tyr(Me)-OH、Fmoc-Tyr(PO3Bzl2)-OH、Fmoc-Tyr(SO3H)-OH、Fmoc-Tyr(SO3Na)-OH·H2O、Fmoc-Tyr(tBu)-OH、Fmoc-Tyr(tBu)-OPfp、Fmoc-Tyr(tBu)-pNA、Fmoc-Tyr(tBu)-Ser[Psi(MeMe)Pro]-OH、Fmoc-Tyr(tBu)-Thr[Psi(MeMe)Pro]-OH、Fmoc-Tyr-OBzl、Fmoc-Tyr-OH、Fmoc-Tyr-OMe、Fmoc-Tyrosinol(tBu)、Fmoc-Tyr-OtBu、Fmoc-Val-Cl、Fmoc-Val-Gly-OH、Fmoc-Valinol、Fmoc-Val-OH、Fmoc-Val-OPfp、Fmoc-Val-Ser[Psi(MeMe)Pro]-OH、Fmoc-Val-Thr[Psi(MeMe)Pro]-OH、Fmoc-β-Ala-OH、Fmoc-β-Ala-OPfp、Fmoc-β-cyclopropyl-L-Alanine、Fmoc-β-D-HoTyr(tBu)-OH、Fmoc-β-HoAla-OH、Fmoc-β-HoArg(Pbf)-OH、Fmoc-β-HoAsn(Trt)-OH、Fmoc-β-HoAsp(OtBu)-OH、Fmoc-β-HoGln(Trt)-OH、Fmoc-β-HoGlu(OtBu)-OH、Fmoc-β-HoIle-OH、Fmoc-β-HoLeu-OH、Fmoc-β-HoLys(Boc)-OH、Fmoc-β-HoMet-OH、Fmoc-β-HoPhe-OH、Fmoc-β-HoPro-OH、Fmoc-β-HoSer(Bzl)-OH、Fmoc-β-HoSer(tBu)-OH、Fmoc-β-HoThr(tBu)-、 OH、Fmoc-β-HoTrp(Boc)-OH、Fmoc-β-HoTyr(tBu)-OH、Fmoc-β-HoVal-OH、Fmoc-γ-Abu-OH、Fmoc-ε-Acp-OH-、For-Ala-OH-DL-Trp-For Et、For-Gly-OH、For-Met-OH、For-Val-OH、H-1-Nal-OH、H-2-Nal-OH·HCl、H-2-Pal-OH·2HCl、H-3-Pal-OH·2HCl-H-OM·3H4-HCal OH·HBr、H-4-Pal-OH·2HCl、H-5-Ava-OH、H-Ash-Gly-OH、H-Ash-NH2·HCl、 H-Abu-OH、H-Abu-OtBu·HCl、H-Acpc-OEt·HCl、H-Aib-OEt·HCl、H-Aib-OH、 H-Aib-OMe·HCl、H-Aib-OtBu·HCl、H-Ala-Ala-OH、H-Ala-Ala-OMe·HCl、H-Ala-AMC·HCl、H-Ala-Glu-OH、H-Ala-NH2·Hl-HCl-AB-z、H-A zl·TosOH、H-Ala-OcHex·HCl、H-Ala-OcHex·TosOH、H-Ala-OH、H-Ala-OiPr·HCl、H-Ala-OMe·HCl、H-Ala-OtBu·HCl、p·H-AHCl、La、Ala H-Ala-Pro-OMe·HCl、H-Ala-Trp-OH、H-Ala-Tyr-OH、H-Arg(Mtr)-OH·1 / 2H 2O、H-Arg(NO2)-OBzl·HCl、H-Arg(NO2)-OH、H-Arg(NO2)-OMe·HCl、H-Arg( Pbf)-NH2、H-Arg(Pbf)-OH、H-Arg(Pbf)-OMe·HCl、H-Arg(Tos)-OH、H-Arg -NH2·2HCl、H-Arg-OEt·2HCl、H-Arg-OH、H-Arg-OH·HCl、H-Arg-OMe·2HCl、 H-Arg-OtBu·2HCl、H-Arg-pNA·2HCl、H-Asn(Trt)-OH·H2O、H-Asn-OH、H-As n-OMe·HCl、H-Asn-OtBu、H-Asp(OBzl)-NH2·HCl、H-Asp(OBzl)-OBzl·HCl、H-Asp(OBzl)-OBzl·TosOH、H-Asp(OBzl)-OH、H-Asp(OBzl)-OtBu·HCl、H-Asp(OBzl)-pNA·HCl、H-Asp(OcHex)-OH、EH·OH-HCpA-O、 Me)-OH、H-Asp(OMe)-OH·HCl、H-Asp(OMe)-OMe·HCl、H-Asp(OMe)-OtBu·HCl、H-Asp(OtBu)-OH、H-Asp(OtBu)-OMe·HCl、H·Bu)Bul-O(t Asp-OBzl、H-Asp-OMe、H-Asp-OtBu、H-Bpa-OH、H-Cha-NH2、H-Cha-OMe·H Cl、H-Chg-OH、H-Chg-OMe·HCl、H-Chg-OtBu·HCl、H-Cit-OH、H-Cys(Acm)- NH2·HCl、H-Cys(Acm)-OH·、H-Cys(Acm)-OH·HCl、H-Cys(Boc)-OMe·HCl、H -Cys(Bzl)-OH、H-Cys(Bzl)-OMe·HCl、H-Cys(Dpm)-OH、H-Cys(Me)-OH、H- Cys(pMeOBzl)-OH、H-Cys(tBu)-OH·HCl、H-Cys(tBu)-OtBu·HCl、H-Cys(Trt)-NH2、H-Cys(Trt)-OHl、H-Cys(Trt)-OMe·HCl(Bu·rt、H-Cl 、H-Cys(Z)-OH、H-Cys(Z)-OH·HCl、H-Cys-NH2·HCl、H-Cys-OEt·HCl、H-Cy s-OH、H-Cys-OMe·HCl、HD-1-Nal-OH、HD-1-Nal-OH·HCl、HD-2-Nal-OH、HD -2-Nal-OH·HCl、HD-2-Pal-OH·2HCl、HD-3-Pal-OH·2HCl、HD-4-Pal-OH·2 HCl、H-Dab(Z)-OH、H-Dab·HBr、H-Dab-OH·HCl、HD-Abu-OEt·HCl、HD-Abu- OH、HD-Ala-NH2·HCl、HD-Ala-OBzl·TosOH、HD-Ala-OH、HD-Ala-OiPr·HCl 、HD-Ala-OMe·HCl、HD-Ala-OtBu·HCl、HD-Allo-Ile-OH、H-Dap(Boc)-OH、H-Dap-OH·HBr、H-Dap-OH·HCl、HD-Arg(NO2)-OH、HD-Arg(Pbf)-OH、HD-Arg-NH2·2HCl、HD-Arg-OH、HD-Arg-OH·HCl、HD-Arg-OMe·H sn-OH·H2O、HD-Asp(OBzl)-OBzl·HCl、HD-Asp(OBzl)-OBzl·TosOH、HD-Asp(OBzl)-OH、HD-Asp(OEt)-OEt·HCl、HD-A (OMe)-OMe·HCl、HD-Asp(OtBu)-OH、HD-Asp(OtBu)-OMe·HCl、HD-Asp(OtBu)-OtBu·HCl、HD-Asp-OBzl、HD-Asp-OH、HD-Asp-OMe-OtBu-OH 、HD-Asp-OtBu·HCl、HD-Bip(44′)-OH·HCl、HD-Bpa-OH、HD-Chg-OH、HD-Cit-OH、HD-Cys(Acm)-OH·HCl、HD-Cys(pMeOBzl)-OBzl-OH·HCl s(Trt)-OH、HD-Cys-OEt·HCl、HD-Cys-OH·H2O·HCl、HD-Cys-OMe·HCl、HD-Dab-OH·2HCl、H-Deg-OH、HD-Gln(Trt)-OH·H u(OBzl)-OBzl·HCl、HD-Glu(OBzl)-OH、HD-Glu(OEt)-OEt·HCl、HD-Glu(OMe)-OH、HD-Glu(OMe)-OMe·HCl、HD-Glu(OtBu)-OH-OH-BuGlu OMe·HCl、HD-Glu(OtBu)-OtBu·HCl、HD-Glu-OBzl、HD-Glu-OBzl·HCl、HD-Glu-OH、HD-Glu-OtBu、HD-Gly(Allyl)-OH、HD-GOH(allyl)-l·HCl 、HD-His(Trt)-OH、HD-His-OH、HD-HoArg-OH、HD-HoCys-OH、HD-HoPhe-OH、HD-HoPro-OH、HD-HoPro-OMe·HCl、HD-HoSer-OH-OH-Nal-OHH-DL-3-Pal-OH·2HCl、H-DL-Ala-OMe·HCl、H-DL-Arg-OH·HCl、H-DL-Asp(OBzl)-OH、H-DL-Asp(OMe)-OMe·HCl、H-DL-Asp(OtBu)-OMe·HCl、H-DL-Asp-OMe、H-DL-Dab·2HCl、H-D-Leu-Gly-OH、H-D-Leu-Leu-OH、H-D-Leu-NH2·HCl、H-D-Leu-OBzl·TosOH、H-D-Leu-OEt·HCl、H-D-Leu-OH、H-D-Leu-OMe·HCl、H-D-Leu-OtBu·HCl、H-DL-Glu(OMe)-OMe·HCl、H-DL-His-OH、H-DL-HoPhe-OH、H-DL-HoPhe-OMe·HCl、H-DL-HoSer-OH、H-DL-Ile-OH、H-DL-Leu-NH2·HCl、H-DL-Leu-OMe·HCl、H-DL-Lys(Fmoc)-OH、H-DL-Lys-OMe·2HCl、H-DL-Met-OH、H-DL-Met-OMe·HCl、H-DL-Nip-OH、H-DL-Nle-OH、H-DL-N-Me-Val-OH、H-DL-Nva-OH、H-DL-Orn-OH·HCl、H-DL-Phe(3-Br)-OH、H-DL-Phe(3-CN)-OH、H-DL-Phe(3-F)-OH、H-DL-Phe(4-Cl)-OH、H-DL-Phe(4-Cl)-OH·HCl、H-DL-Phe(4-Cl)-OMe·HCl、H-DL-Phe(4-I)-OH、H-DL-Phe(4-Me)-OH、H-DL-Phe(4-NO2)-OH·H2O、H-DL-Phe-OEt·HCl、H-DL-Phe-OMe·HCl、H-DL-Phg(2-Cl)-OH、H-DL-Phg-OH、H-DL-Pra-OH、H-DL-Pro-NH2、H-DL-Pro-OH、H-DL-Ser(Bzl)-OH、H-DL-Ser-OEt·HCl、H-DL-Ser-OMe·HCl、H-DL-Ser-OtBu·HCl、H-DL-Tle-OH、H-DL-Trp-NH2、H-DL-Trp-OMe·HCl、H-DL-Tyr(Me)-OH、H-DL-Tyr-OMe·HCl、H-DL-Val-OEt·HCl、H-DL-Val-OMe·HCl、HD-Lys(Boc)-OtBu·HCl、HD-Lys(Fmoc)-OH、HD-Lys(Tfa)-OH、HD-Lys(Z)-OMe·HCl、HD-Lys(Z)-OtBu·HCl、HD-Lys-OBzl·HCl·HCl·HDOHY s-OH·HCl、HD-Lys-OMe·2HCl、HD-Met-OEt·HCl、HD-Met-OH、HD-Met-OMe·HCl、HD-Nle-OH、HD-Nle-OMe·HCl、HDN-Me-Leu-OMe·H e-Pro-OH、HDN-Me-Val-OH·HCl、HDN-Me-Val-OMe·HCl、HD-Nva-OEt·HCl、HD-Orn(Boc)-OH、HD-Orn(Z)-OH、HD-Orn-OH·HCl-PH-PH he(2,4-Dime)-OH、HD-Phe(2,5-DiCl)-OH、HD-Phe(2,6-DiCl)-OH、HD-Phe(2-Br)-OH、HD-Phe(2-Cl)-OH·HCl、HD-Phe(2-F)-OH·H·HCl (3,4-DiCl)-OH、HD-Phe(3,4-DiF)-OH、HD-Phe(3,5-DiF)-OH、HD-Phe(3-Br)-OH、HD-Phe(3-Br)-OH·HCl、HD-Phe(3-Cl)-OH-H-Phe(4-Br) -OH、HD-Phe(4-CF3)-OH·HCl、HD-Phe(4-Cl)-OH、HD-Phe(4-Cl)-OH·HCl、HD-Phe(4-Cl)-OMe·HCl、HD-Phe(4-CN)-OH、HD-Phe(4-Cl)-OH·HCl HD-Phe(4-I)-OH、HD-Phe(4-Me)-OH、HD-Phe(4-NO2)-OH·H2O、HD-Phe(4-NO2)-OMe·HCl、HD-Phe-AMC·HCl、HD-Phe-NH2·HCl、HD-OH·Hz Cl、HD-Phe-OH、HD-Phe-OMe·HCl、HD-Phe-OtBu·HCl、HD-Phe-pNA、HD- Phg(4-Cl)-OH、HD-Phg(4-Cl)-OH·HCl、HD-Phg-AMC·HCl、HD-Phg-NH2、HD-Phg-OH、HD-Phg-OMe·HCl、HD-Phg-OtBu·HCl、HD-Pra-OH、HD-Pro-NH2、HD-Pro-NH2·HCl、HD-Pro- OBzl·HCl、HD-Pro-OH、HD-Pro-OMe·HCl、HD-Pro-OtBu、HD-Pro-OtBu·HCl、HD-Pyr-OEt、HD-Ser(Bzl、 )-OH、HD-Ser(Bzl)-OH·HCl、HD-Ser(tBu)-OBzl·HCl、HD-Ser(tBu)-OH、HD-Ser(tBu)-OMe·HCl、HD-Ser(tBu)-OtBu·HCl-HCl D-Ser-OH、HD-Ser-OMe·HCl、HD-Thr(Me)-OH、HD-Thr(tBu)-OH、HD-Thr (tBu)-OMe·HCl、HD-Thr-OBzl、HD-Thr-OBzl·HCl、HD-Thr-OH、HD-Thr-O Me·HCl、HD-Tic-OH、HD-Tle-OH、HD-Tle-OMe·HCl、HD-Trp(Boc)-OH、HD -Trp-OBzl·HCl、HD-Trp-OEt·HCl、HD-Trp-OH、HD-Trp-OMe·HCl、HD-Tyr (3,5-DiBr)-OH·2H2O、HD-Tyr(3-Cl)-OH、HD-Tyr(3-I)-OH、HD-Tyr(Bzl)-OH、HD-Tyr(tBu)-OH、HD-Tyr(tBu)-OtBu·HCl-HD-H-H-Tyr NH2·HCl、HD-Tyr-OEt·HCl、HD-Tyr-OH、HD-Tyr-OMe、HD-Tyr-OMe·HCl、 HD-Tyr-OtBu、HD-Val-OBzl·TosOH、HD-Val-OEt·HCl、HD-Val-OH、HD-Va l-OMe·HCl、HD-Val-OtBu·HCl、H-gamma-Glu-Glu-OH、H-Gln(Trt)-OH· H2O、H-Gln-OBzl、H-Gln-OH、H-Gln-OMe·HCl、H-Gln-OtBu·HCl、H-Gln-p NA、H-Glu(Gly-him)-OH、H-Glu(OAll)-OAll、H-Glu(OBzl)-NCA、H-Glu(OBzl)-OBzl·HCl、H-Glu(OBzl)-OBzl·TosOH、H-Glu(OBzl)-Glu(OAll)-H OBzl)-OH·HCl、H-Glu(OBzl)-OtBu·HCl、H-Glu(OcHex)-OBzl·HCl、H-Glu(OcHex)-OH、H-Glu(OEt)-OEt·HCl、H-Glu(OEt)-OH、Glu(GOH-OH)H-Glu(OMe)-OMe·HCl、H-Glu(OMe)-OtBu·HCl、H-Glu(OtBu)-NH2·HCl、H-Glu(OtBu)-OBzl·HCl、H-Glu(OtBu)-OH、H-Glu(OtBu)-OMe·HCl、H-Glu(OtBu)-OtBu·HCl、H-Glu-Gly-OH、H-Glu-OBzl、H-Glu-OBzl·HCl、H-Glu-OEt、H-Glu-OH、H-Glu-OMe、H-Glu-OtBu、H-Glu-OtBu·HCl、H-Glu-pNA、H-Gly-Ala-Gly-OH·HCl、H-Gly-AMC·HCl、H-Gly-Asn-OH、H-Gly-Asp-OH、H-Gly-Gly-Ala-OH·HCl、H-Gly-Gly-Gly-OH、H-Gly-Gly-OMe·HCl、H-Gly-Gly-Phe-OH、H-Gly-Hyp-OH、H-Gly-Met-OH、H-Gly-NH2·AcOH、H-Gly-NH2·HCl、H-Gly-OBzl·HCl、H-Gly-OBzl·TosOH、H-Gly-OEt·HCl、H-Gly-OH、H-Gly-Oipr·HCl、H-Gly-OMe·HCl、H-Gly-OtBu·AcOH、H-Gly-OtBu·HCl、H-Gly-Phe-OH、H-Gly-pNA·HCl、H-Gly-Trp-OH、H-Gly-Val-OH、H-Gly-Val-OH·HCl、H-His(1-Me)-OH、H-His(1-Me)-OH·2HCl、H-His(1-Me)-OMe·HCl、H-His(Trt)-OH、H-His(Trt)-OMe·HCl、H-His-NH2·2HCl、H-His-OH、H-His-OMe·2HCl、H-HoArg-OH、H-HoArg-OH·HCl、H-HoArg-OMe·2HCl、H-HoPhe-OEt·HCl、H-HoPhe-OH、H-HoPhe-OMe·HCl、H-HoPro-OH、H-HoSer-OH、H-HoTyr-OH·HBr、H-Hyp(Bzl)-OH·HCl、H-Hyp(tBu)-OH、H-Hyp(tBu)-OtBu·HCl、H-Hyp-OBzl、H-Hyp-OBzl·HCl、H-Hyp-OEt·HCl、H-Hyp-OH、H-Hyp-OMe·HCl、H-Ile-NH2·HCl、H-Ile-OAll·TosOH、H-Ile-OEt·HCl、H-Ile-OH、H-Ile-OMe·HCl、H-Ile-OtBu·HCl、H-Leu-Ala-OH、H-Leu-CMK·HCl、H-Leu-Gly-OH、Leu-H-H·H Cl、H-Leu-Leu-OMe·HCl、H-Leu-NH2·HCl、H-Leu-OAll·TosOH、H-Leu-OBzl ·TosOH、H-Leu-OEt·HCl、H-Leu-OH、H-Leu-OMe·HCl、H-Leu-OtBu、H-Leu-O tBu·HCl、H-Leu-pNA·HCl、H-Lys(2-Cl-Z)-OH、H-Lys(Ac)-OH、H-Lys(Ac)-OH·HCl、H-Lys(Alloc)-OH、H-Lys(Biotinyl)-OH、H-H-Boc-H-H(H2) (Boc)-OBzl·HCl、H-Lys(Boc)-OBzl·TosOH、H-Lys(Boc)-OH、H-Lys(Boc)-OMe·HCl、H-Lys(Boc)-OtBu·HCl、H-Lys(Butyryl)-OH、H-Lys(Oyl) H·HCl、H-Lys(Crotonyl)-OH、H-Lys(Dnp)-OH·HCl、H-Lys(Fmoc)-OH、H-Lys(Fmoc)-OH·HCl、H-Lys(Fmoc)-OMe·HCl、H-Lys(FrucTosyl)-OH-Lys(Fmoc)-OH ropionyl)-OH、H-Lys(Suc)-OH·HCl、H-Lys(Tfa)-NCA、H-Lys(Tfa)-OH、H-Lys(Z)-NH2·HCl、H-Lys(Z)-OBzl·HCl、H-Lys(Z)-OBzl·H-H(H-Hz) OH、H-Lys(Z)-OMe·HCl、H-Lys(Z)-OtBu·HCl、H-Lysinol(Z)·HCl、H-Lys-OBzl·HCl·TosOHTosOH、H-Lys-OEt·2HCl、H-Lys-OHL·2HL·HCl、H-HCl -Lys-OMe·2HCl、H-Met(O)-OH、H-Met-NH2·HCl、H-Met-OAll·TosOH、H-Met -OEt·HCl、H-Met-OH、H-Met-OiPr·HCl、H-Met-OMe·HCl、H-Met-OtBu·HCl、H-Nle-NH2·HCl、H-Nle-OBzl·TosOH、H-Nle-OH、H-Nle-OMe·HCl、H-Nle-OtBu·HCl、HN-Me-Aib-NH2、HNle-Me-AH-Me OH·HCl、HN-Me-Ala-OMe·HCl、HN-Me-D-Ala-OH·HCl、HN-Me-Ile-OH、HN-Me-Leu-OBzl·TosOH、HN-Me-Phe-OH·HCl、HN-Me-Pro-OH、HN-H-H N-Me-Ser-OH·HCl、HN-Me-Val-OH·HCl、H-Nva-OEt·HCl、H-Nva-OMe·HCl、H-Nva-OtBu·HCl、H-Orn(2-Cl-Z)-OH、H-Orn(Boc)-HCOl·H )-OMe·HCl、H-Orn(Tfa)-OH、H-Orn(Z)-OH、H-Orn(Z)-OMe·HCl、H-Orn(Z) -OtBu·HCl、H-Orn-AMC·HCl、H-Orn-OH·HCl、H-Orn-OMe·2HCl、H-Phe(2,4 -DiCl)-OH、H-Phe(2,4-Dime)-OH、H-Phe(2,5-DiCl)-OH、H-Phe(2,6-DiCl)-OH、H-Phe(2-Br)-OH、H-Phe(2-Cl)-OH、H-Phe(2-Phe(2,4-Dime)-H-H )-OH、H-Phe(3,4-DiCl)-OH、H-Phe(3,4-DiCl)-OMe·HCl、H-Phe(3-Br)-O H、H-Phe(3-Cl)-OH、H-Phe(3-Cl)-OH·HCl、H-Phe(3-CN)-OH、H-Phe(4-Br )-OH、H-Phe(4-Br)-OH·HCl、H-Phe(4-Br)-OMe·HCl、H-Phe(4-CF3)-OH、H-Phe(4-Cl)-OH、H-Phe(4-Cl)-OH·HCl、H-CN-Phe(4-Br)-OH-F-H-H 、H-Phe(4-I)-OH、H-Phe(4-Me)-OH、H-Phe(4-Me)-OH·HCl、H-Phe(4-NH -OH、H-Phe(4-NH2)-OH·HCl、H-Phe(4-NO2)-OEt·HCl、H-Phe(4-NO2)-OH、H-Phe(4-NO2)-OH·H2O、H-Phe(4-NO2)-OMe·HCl、H-Phe-Ala-OH、H-Phe-Gl y-OH、H-Phe-Leu-OH、H-Phe-NH2、H-Phe-NH2·HCl、H-Phe-NHNH2、H-Phe-OA ll·TosOH、H-Phe-OBzl·HCl、H-Phe-OEt·HCl、H-Phe-OH、H-Phe-OMe·HCl、H -Phe-OtBu·HCl、H-Phe-Phe-OH、H-Phe-pNA、H-Phg(4-Cl)-OH、H-Phg(4-OH) -OEt、H-Phg(4-OH)-OH、H-Phg-AMC·HCl、H-Phg-NH2·HCl、H-Phg-OH、H-Phg -OtBu·HCl、H-Pra-OH、H-Pra-OMe·HCl、H-Pro-Gly-OH、H-Pro-Hyp-OH、H-P ro-NH2、H-Pro-NHEt·HCl、H-Pro-NMe2、H-Pro-OBzl·HCl、H-Pro-OH、H-Pro-Oipr·HCl、H-Pro-OMe·HCl、H-Pro-OtBu、H-Pro-pNA·H r-OEt·HCl、H-Pyr-OH、H-Pyr-OtBu、H-Sar-NH2·HCl、H-Sar-OEt·HCl、H-Ca r-OMe·HCl、H-Sar-OtBu·HCl、H-Ser(Ac)-OH、H-Ser(Bzl)-OBzl·HCl、H-Se r(Bzl)-OH、H-Ser(Bzl)-OH·HCl、H-Ser(Bzl)-OMe·HCl、H-Ser(tBu)-NH2· HCl、H-Ser(tBu)-OBzl·HCl、H-Ser(tBu)-OH、H-Ser(tBu)-OMe·HCl、H-Ser- NH2·HCl、H-Ser-NHMe、H-Ser-OBzl·HCl、H-Ser-OEt·HCl、H-Ser-OH、H-Ser -OMe·HCl、H-Ser-OtBu·HCl、H-Thr(Bzl)-OBzl·HCl、H-Thr(Bzl)-OBzl·oxa late、H-Thr(Bzl)-OH·HCl、H-Thr(Me)-OH、H-Thr(tBu)-NH2·HCl、H-Thr(t Bu)-OH、H-Thr(tBu)-OMe·HCl、H-Thr(tBu)-OtBu、H-Thr(tBu)-OtBu·AcOH、H-Thr(tBu)-OtBu·HCl、H-Thr-OBzl、H-Thr-OBzl·HCl、H-Thr-OBzl·oxalate、H-Thr-OH、H-Thr-OMe、H-Thr-OMe·HCl、H-Thr-OtBu、H-Thr-OtBu·HCl、H-Tle-OH、H-Tle-OMe·HCl、H-Tle-OtBu·HCl、 H-Trp(Boc)-OH、H-Trp-AMC·2HCl、H-Trp-NH2·HCl、H-Trp-OBzl·HCl、H-Tr p-OEt·HCl、H-Trp-OH、H-Trp-OMe·HCl、H-Tyr(3,5-DiI)-OH、H-Tyr(3,5-D iNO2)-OH、H-Tyr(35-DiBr)-OH·2H2O、H-Tyr(35-DiCl)-OH、H-Tyr(3-Cl)- OH、H-Tyr(3-I)-OH、H-Tyr(3-NH2)-OH·2HCl、H-Tyr(3-NO2)-OH、H-Tyr(3- NO24-SO3H)-OH、H-Tyr(Ac)-OH、H-Tyr(Bzl)-OBzl·HCl、H-Tyr(Bzl)-OH、H -Tyr(Bzl)-OMe、H-Tyr(Bzl)-OMe·HCl、H-Tyr(H2PO3)-OH、H-Tyr(Me)-OH、 H-Tyr(Propargyl)-OH、H-Tyr(tBu)-NH2、H-Tyr(tBu)-OH、H-Tyr(tBu)-OMe·HCl、H-Tyr(tBu)-OtBu·HCl、H-Tyr(Tos)-OH、H·H2-Tyr-Tyr-Tyr 、H-Tyr-OBzl、H-Tyr-OBzl·HCl、H-Tyr-OBzl·TosOH、H-Tyr-OEt·HCl、H-Ty r-OH、H-Tyr-OMe、H-Tyr-OMe·HCl、H-Tyr-OtBu、H-Tyr-pNA、H-Val-Ala-OH 、H-Val-Ala-OH·HCl、H-Val-NH2·HCl、H-Val-OBzl·HCl、H-Val-OBzl·TosO H、H-Val-OEt·HCl、H-Val-OH、H-Val-Oipr·HCl、H-Val-OMe·HCl、H-Val-OtB u·HCl、H-Val-pNA、H-Val-Trp-OH、H-β-Ala-NH2·HCl、H-β-Ala-OBzl·TosO H、H-β-Ala-OEt·HCl、H-β-Ala-OH、H-β-Ala-OMe·HCl、H-β-Ala-OtBu·HCl、 H-β-HoAla-OH·HCl、H-β-HoAsp·HCl、H-β-HoGln-OH·HCl、H-β-HoGlu-OH·HCl、H-β-HoIle-OH·HCl、H-β-HoLeu-OH·HCl-OH-OH-OH VAl-HoPheH-γ-Abu-OBzl·TosOH、H-γ-Abu-OMe·HCl、H-γ-Abu-OtBu·HCl、Ivdde-Lys(Boc)-OH、L-Alaninol、L-Cysteinol(Bzl)、L-Cysteinol(pMeBzl)、L-Homoserine lactone、L-Isoleucinol、L-Leucinol(oil)、L-Methioninol、L-Norvalinol、L-Phenylalaninol、L-Phenylglycinol、L-Prolinol、L-Serinol(Bzl)、L-Threoninol、L-Threoninol(Bzl)、L-Threoninol(Bzl)·HCl、L-Tryptophanol、L-Tyrosinol、L-Tyrosinol·HCl、L-Valinol、Moc-Val-OH、Mpa(Acm)、Mpa(Bzl)、Mpa(MMt)-OH、Mpa(Trt)、Mpa(Trt)-OSu、N-Boc-cis-4-hydroxy-D-Proline、N-Formyl-Leu-OH、NH2-NTA(Me)3·HBr、N-Phthaloyl-Phenylalanine、Pal-Glu(OtBu)-OH、Pal-Glu-OtBu、Pbf-NH2、PhC3H6-Lys(Boc)-OH、Pht-Dopa-OH、Tfa-Gly-OH、Thioanisole、Tos-Ala-OH、Tos-Arg-OH、Tos-Arg-OMe·HCl、Tos-D-Pro-OH、Tos-D-Val-OH、Tos-Gly-OMe、Tos-Lys(Boc)-OH、Tos-Phe-OH、Tos-Pro-OH、Tos-Val-OH、Trans-4-hydroxy-L-prolinol·hydrochloride、Trt-Cys(Trt)-OH·DEA、Trt-Cys(Trt)-OSu、Trt-D-Cys(Trt)-OH·DEA、Trt-D-Ser-OH、Trt-Gly-OH、Trt-Ser-OH、Trt-Ser-OMe、Trt-Thr-OH·DEA、Z(2-Br)-OSu、Z(4-NO2)-OSu、Z-Abu-OH、Z-Aib-OH、Z-Ala-Ala-OH、Z-Ala-Gly-OH、Z-Ala-NH2、Z-Ala-OH、Z-Ala-OMe、Z-Ala-OSu、Z-Ala-Trp-OH, Z-Arg(Mbs)-OH·DCHA, Z-Arg(Mtr)-OH·CHA, Z-Arg(NO2)-OH, Z-Arg(Pbf)-OH·CHA, Z-Arg(Pbf)-OH·DCHA, Z-Arg(Z)2-OH, Z-Arg-OH, Z-Arg-OH·HBr, Z-Arg-OH·HCl, Z-Asn(Trt)-OH, Z-Asn-OH, Z-Asn-ONp, Z-Asp(OBzl)-OH, Z-Asp(OBzl)-OSu, Z-Asp(OMe)-OH, Z-Asp(OMe)-OtB u, Z-Asp(OtBu)-OBzl, Z-Asp(OtBu)-OH·DCHA, Z-Asp(OtBu)-OH·H2O, Z-Asp(OtBu)-OMe, Z-Asp(OtBu)-OSu, Z-Asp-OBzl, Z-Asp-OH, Z-Asp-OMe, Z-Asp-OMPe, Z-Asp-OtBu, Z-Asp-OtBu·DCHA, Z-Cha-OH, Z-Cha-OH·DCHA, Z-Chg-OH, Z-Cys(pMeOBzl)-OH, Z-Cys(Trt)-OH, Z-Cys(Z)-OH, Z-Na-2-Na l-OH、ZD-Abu-OH、ZD-Ala-Gly-OH、ZD-Ala-NH2、ZD-Alaninol、ZD-Ala-OH、Z-Dap(Boc)-OH、Z-Dap(Fmoc)-OH、Z-Dap-OH、ZD-Arg(Mtr)-OH·CHA、Z D-Arg(Pbf)-OH·CHA、ZD-Arg-OH、ZD-Arg-OH·HCl、ZD-Asn(Trt)-OH、ZD-Asn-OH、ZD-Asp(OtBu)-OH·H2O、ZD-Asp-OH、ZD-Asp-OMe、ZD-Cha-OH、ZD- Chg-OH、ZD-Dap(Boc)-OH、ZD-Dap(Boc)-ol、ZD-Dap-OH、ZD-Gln-OH、ZD-Glu(OBzl)-OH、ZD-Glu(OtBu)-OH、ZD-Glu-OBzl、ZD-Glu-OEt、ZD-Glu-OH 、ZD-Glu-OMe、ZD-His-OH、Z-DL-Ala-OH、Z-DL-Asn-OH、Z-DL-Asp-OH、ZD-Leu-OH、ZD-Leu-OH·DCHA、Z-DL-Glu-OtBu、Z-DL-His-OH、Z-DL-Met-OH、Z-DL-Nva-OH、Z-DL-Phe(4-Cl)-OH、Z-DL-Val-OH、ZD-Lys(Boc)-OH、ZD-Lys(Boc)-OH·DCHA、ZD-Lys(Boc)-OSu、ZD-Lys-OH、ZD-Met-OH、ZDN-Me- Val-OH、ZD-Nva-OH、ZD-Orn-OH、ZD-Phe(4-F)-OH、ZD-Phenylalanine、ZD-Phe-OH、ZD-Phg-OH、ZD-Pro-OH、ZD-Pyr-OH、ZD-Ser(tBu)-OH、ZD-Se r(tBu)-OMe、ZD-Ser-OH、ZD-Ser-OMe、ZD-Thr-OH、ZD-Thr-OMe、ZD-Trp(Boc)-OH、ZD-Trp(Boc)-OH·DCHA、ZD-Trp-OH、ZD-Trp-OSu、ZD-Tyr(Bzl) -OH、ZD-Tyr(tBu)-OH·DCHA、ZD-Tyr-OH、ZD-Val-OH、Z-Gln(Trt)-OH、Z-Gln-OH、Z-Gln-OMe、Z-Gln-ONp、Z-Glu(OBzl)-OH、Z-Glu(OBzl)-OH·DCHA 、Z-Glu(OSu)-OBzl、Z-Glu(OtBu)-OBzl、Z-Glu(OtBu)-OH、Z-Glu(OtBu)-OH·DCHA、Z-Glu(OtBu)-OMe、Z-Glu(OtBu)-OSu、Z-Glu-OBzl、Z-Glu-OB zl·DCHA、Z-Glu-OH、Z-Glu-OMe、Z-Glu-OtBu、Z-Glycinol、Z-Gly-NH2、Z-Gly-OH、Z-Gly-OMe、Z-Gly-OSu、Z-Gly-Phe-NH2、Z-Gly-Pro-OH、Z-His( Dnp)-OH, Z-His(Trt)-OH, Z-His(Z)-OH·EtOH, Z-His-OH, Z-His-OMe, Z-HoArg(NO2)-OH, Z-HoArg-OH, Z-HoSer-OH, Z-Hyp(tBu)-OMe, Z-Hyp-OH, Z-Hyp-OMe, Z-Ile-OH, Z-Ile-OSu, ZL-2-Nal-OH, Z-Leu-Leu-OH, Z-Leu-OH, Z-Leu-OH·DCHA, Z-Lys(Boc)(Isopropyl)-OH·DCHA, Z-Lys(Boc)-OH,Z-Lys(Boc)-ONp, Z-Lys(Boc)-OSu, Z-Lys(For)-OH, Z-Lys(Tfa)-OH, Z-Lys(Z)-OH, Z-Lys(Z)-OSu, Z-Lys-OH, Z-Lys-OMe·HCl, Z-Met-OH, Z-Met-OMe, ZN-Me-Ala-OH, ZN-Me-Glu(OtBu)-OH, ZN-Me-Ile-OH, ZN-Me-Phe-OH, ZN-Me-Ser-OH, ZN-Me-Val-OH, Z-Nva-OH, Z-Orn(Alloc)-OH·DCHA, Z-Orn(Boc )-OH、Z-Orn(Z)-OH·DCHA、Z-Orn-OH、Z-Orn-OH·HCl、Z-Phe(4-F)-OH、Z-Phe-NH2、Z-Phenylalaninol、Z-Phe-OH、Z-Phe-OMe、Z-Phe-OSu、Z-Phg-OH、Z -Pra-OH、Z-Prolinol、Z-Pro-NH2、Z-Pro-OH、Z-Pro-OSu、Z-Pyr-OH、Z-Pyr-OSu、Z-Pyr-OtBu、Z-Sar-NH2、Z-Sar-OH、Z-Ser(Bzl)-OH、Z-Ser(TBDMS)- OH、Z-Ser(tBu)-NH2、Z-Ser(tBu)-OH、Z-Ser(tBu)-OMe、Z-Ser(Tos)-OMe、Z-Ser(Trt)-OH、Z-Ser-NH2、Z-Ser-NHNH2、Z-Ser-OBzl、Z-Ser-OH、Z-Ser-OH OMe、Z-Thr(Me)-OH、Z-Thr(tBu)-OH、Z-Thr(tBu)-OH·DCHA、Z-Threoninol、Z-Thr-NH2、Z-Thr-OBzl、Z-Thr-OH、Z-Thr-OMe、Z-Tic-OH、Z-Tle-OH、Z-Tle-OH le-OH·DCHA, Z-Trp(Boc)-OH, Z-Trp(Boc)-OH·DCHA, Z-Trp-OBzl, Z-Trp-OH, Z-Trp-OMe, Z-Tyr(Bzl)-OH, Z-Tyr(tBu)-OH, Z-Tyr(tBu)-OH·DCHA, Z-Tyr(tBu)-OMe, Z-Tyr-OH, Z-Tyr-OMe, Z-Tyr-OtBu·H2O, Z-Tyr-Tyr-OH, Z-Val-Ala-OH, Z-Val-NH2, Z-Val-OEt, Z-Val-OH, Z-Val-OSu, Z-Val-Ser-OH,Z-β-Ala-OH, Z-β-Ala-OSu, Z-γ-Abu-OH, Z-ε-Acp-OH, etc.

[0021] In the present invention, the "pyrrolidine (Pyrrolysine, Pyl; O)" is represented by the chemical formula C 12 H 21 N 3 O 3 and is an amino acid used in some methanogenic bacteria.

[0022] In the present invention, the "theanine (gamma-glutamylethylamide)" is represented by the chemical formula C 7 H 14 N 2 O 3 It exists as the isomers of L-theanine and D-theanine, and L-theanine is an amino acid discovered in gyokuro leaves.

[0023] In the present invention, the "gamma-glutamylmethylamide (GMA)" is represented by the chemical formula C 6 H 12 N 2 O 3 It is an amino acid that can be represented by the following formula:

[0024] In the present invention, the "beta-aminobutyric acid" and "gamma-aminobutyric acid (GABA)" are represented by the chemical formula C 4 H 9 NO 2 and the two are isomers.

[0025] In the present invention, the "monosaccharide" refers to the most basic carbohydrate unit that cannot be decomposed into simpler compounds by hydrolysis, and may be glucose, fructose, lactose, etc., or an isomer thereof, but is not limited thereto as long as it can form a polysaccharide through an oxygen-glycosidic bond.

[0026] In the present invention, the "disaccharide" refers to a combination of two monosaccharides such as sucrose, lactose, and maltose, the "oligosaccharide" refers to a combination of 2 to 10 monosaccharides, and the "polysaccharide" refers to a combination of many monosaccharides. The above terms may be used interchangeably and include, without limitation, any polymer in which monosaccharides are linked by oxygen-glycosidic bonds.

[0027] In the present invention, adjacent M and M among the plurality of M may be linked by a bond that can be cleaved in a pH-specific or catalyst-specific manner to form a polymer represented, for example, as "MM...M". The linkage may be, but is not limited to, a disulfide bond, an esterification reaction, a peptide bond reaction, a Claisen condensation reaction, an aldol condensation, or a glycoside bond reaction. In the present invention, each M unit compound may have two or more functional groups therein for the linkage.

[0028] In the present invention, the "disulfide bond" is a covalent bond formed between thiol groups (-SH), and is represented by the general formula RSSR, also called a disulfide bridge. For example, the disulfide bond may be formed by a cysteine ​​unit, but is not limited to any unit having a thiol group.

[0029] In the present invention, the "ester reaction" is a general term for a reaction in which an alcohol or a phenol reacts with an organic acid or an inorganic acid to undergo condensation with loss of water.

[0030] In the present invention, the "peptide bond" or "amide linkage" refers to a bond between a carboxyl group (-COOH) and an amino group (NH 2 This is a chemical bond that forms a covalent amide bond (-CO-NH-) between the carboxyl group and the amino group at the N-terminus, resulting in a dehydration reaction that forms a water molecule during the reaction. This process gives the peptide an amino group at the N-terminus and a carboxyl group at the C-terminus, providing directionality for the peptide.

[0031] In the present invention, M may be represented by the following formula 2, but is not limited thereto.

number

[0032] In the present invention, in the formula 2, X 1 ~X m is independently an amino acid, an amino acid analog, a peptide, or a peptide analog, 1 is N-terminal, X m is at the C-terminus or m is N-terminal, X1 may be at the C-terminus.

[0033] In the present invention, in the formula 2, m may be an integer of 1 to 100, preferably an integer of 2 to 100, more preferably an integer of 2 to 50, and even more preferably an integer of 3 to 15, which prevents the residence time during detection and analysis by chromatography from becoming too short or too long, enabling rapid detection, and allows easy and accurate detection or measurement by methods such as mass spectrometry. On the other hand, when m exceeds 100, the residence time during detection and analysis by chromatography becomes too long, and detection takes an excessively long time.

[0034] In the present invention, the term "retention time (RT)" refers to the time from when a sample is added to a chromatography to when a peak of the component appears.

[0035] In one embodiment of the present invention, the X 1 or the above X m may be isoleucine, lysine, serine, arginine or threonine, and preferably lysine or arginine, but may be any amino acid or amino acid analogue that specifically reacts with a catalyst to cleave the bonds between multiple M and M that form a polymer, without any limitation.

[0036] In another embodiment of the present invention, the X 2 ~X m-1 may each independently be any one selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, threonine, serine, cysteine, aspartic acid, asparagine, glutamic acid, glutamine, phenylalanine, tyrosine, tryptophan, and proline, but includes, without limitation, any amino acid or amino acid analog that does not react with a catalyst that cleaves the bonds between the multiple Ms and Ms that form a polymer.

[0037] In the present invention, among a plurality of M's forming a polymer, the gap between adjacent linked M's is cleaved by a catalyst, and in this case, the catalyst may be an enzyme or a synthetic catalyst.

[0038] In the present invention, the enzyme may be, but is not limited to, a peptide hydrolase, preferably a peptide endohydrolase, or a lactase.

[0039] In the present invention, the "peptidase (protease, proteinase)" is an enzyme that catalyzes the hydrolysis of peptide bonds, and an enzyme that acts on the N-terminus or C-terminus of a peptide chain to release amino acids in the order of bonds is called an exopeptidase, and an enzyme that acts on peptide bonds within a peptide chain is called an endopeptidase. Using the peptide hydrolases, only the peptide bonds of specific amino acids can be specifically hydrolyzed.

[0040] In the present invention, the peptide hydrolase may be one or more selected from the group consisting of trypsin, chymotrypsin, thrombin, plasmin, subtilisin, thermolysin, pepsin, and glutamyl endopeptidase, and preferably one or more selected from the group consisting of trypsin, chymotrypsin, subtilisin, thermolysin, and glutamyl endopeptidase, but is not limited thereto.

[0041] In the present invention, the synthetic catalyst enables an efficient cleavage reaction without being restricted by conditions such as pH and temperature.

[0042] In the present invention, the synthetic catalyst may be, but is not limited to, an artificial metalloenzyme, an organic artificial enzyme, or a reducing agent that breaks disulfide bonds.

[0043] In the present invention, the artificial metalloproteases include, but are not limited to, water-soluble catalysts using copper (II), cobalt (III), iron (III), palladium (II), cerium (IV), etc. as the catalyst center, or copper (II) complex compounds attached to a support.

[0044] In the present invention, the organic artificial proteases may be those having functional groups attached to a silica support or a polystyrene support, but are not limited thereto.

[0045] In the present invention, the reducing agent that cleaves the disulfide bond may be glutathione, thioglycolic acid, or cysteamine, but includes, without limitation, any agent that can reduce the disulfide bond between M and M to a thiol group.

[0046] In the present invention, the first binding portion is capable of detecting or quantifying the analyte by directly or indirectly binding to the analyte, and includes, without limitation, any first binding portion that can specifically or non-specifically bind to the analyte.

[0047] In the present invention, the first binding portion may include one or more selected from the group consisting of a compound that specifically binds to the analyte, a probe, an antisense nucleotide, an antibody, an oligopeptide, a ligand, a PNA (peptide nucleic acid), and an aptamer, but is not limited thereto.

[0048] In the present invention, the "probe" refers to a substance capable of specifically binding to an analyte to be detected in a sample, and a substance capable of specifically confirming the presence of the analyte in a sample through said binding. The type of probe is not limited to a substance commonly used in the art, but may be preferably PNA (peptide nucleic acid), LNA (locked nucleic acid), peptide, polypeptide, protein, RNA or DNA, and most preferably PNA. More specifically, the probe includes a biological material derived from an organism or a similar substance, or a substance produced outside the body, and may be, for example, an enzyme, a protein, an antibody, a microorganism, an animal or plant cell and organ, a nerve cell, DNA, and RNA, and DNA includes cDNA, genomic DNA, and oligonucleotides, RNA includes genomic RNA, mRNA, and oligonucleotides, and examples of proteins include antibodies, antigens, enzymes, peptides, etc.

[0049] In the present invention, the term "LNA (locked nucleic acids)" refers to a nucleic acid analogue containing a 2'-O, 4'-C methylene bridge [J Weiler, J Hunziker and J Hall Gene Therapy (2006) 13, 496.502]. LNA nucleotides contain the general nucleic acid bases of DNA and RNA and can form base pairs according to the Watson-Crick base pairing rules. However, the "locking" of the molecule by the methylene bridge prevents LNA from forming an ideal shape for Watson-Crick binding. When LNA is included in a DNA or RNA oligonucleotide, it can pair with a complementary nucleotide strand more quickly to increase the stability of the double helix.

[0050] In the present invention, the term "antisense" refers to an oligomer having a sequence of nucleotide bases and an intersubunit backbone that allows the antisense oligomer to hybridize to a target sequence in RNA by Watson-Crick base pairing, typically with mRNA, to form an RNA:oligomer heteroduplex within the target sequence. The oligomer can have exact sequence complementarity or approximate complementarity to the target sequence.

[0051] In the present invention, if the gene sequence information of the analyte is known, a person skilled in the art can easily design the primer, the probe, or the antisense nucleotide that specifically binds to the gene based on the gene sequence information.

[0052] In the present invention, the term "antibody (Ab)" refers to a substance that specifically binds to an antigen to cause an antigen-antibody reaction. For the purposes of the present invention, antibody refers to an antibody that specifically binds to the analyte.

[0053] In the present invention, the antibody includes all of polyclonal antibodies, monoclonal antibodies, and recombinant antibodies. The antibody can be easily produced using techniques well known in the art. For example, polyclonal antibodies can be produced by a method well known in the art, including the steps of injecting an antigen of the protein into an animal, collecting blood from the animal, and obtaining serum containing the antibody. Such polyclonal antibodies can be produced from any animal, such as goats, rabbits, sheep, monkeys, horses, pigs, cows, and dogs. In addition, monoclonal antibodies can be produced using the hybridoma method well known in the art [see Kohler and Milstein (1976) European Journal of Immunology 6:511-519] or phage antibody library technology [see Clackson et al., Nature, 352:624-628, 1991; Marks et al., J. Mol. Biol., 222:58, 1-597, 1991]. The antibodies produced by the above method can be separated and purified using methods such as gel electrophoresis, dialysis, salt precipitation, ion exchange chromatography, and affinity chromatography. The antibodies of the present invention include not only intact forms having two full-length light chains and two full-length heavy chains, but also functional fragments of antibody molecules. The functional fragments of antibody molecules refer to fragments that retain at least the antigen-binding function, and include Fab, F(ab'), F(ab')2, and Fv.

[0054] In the present invention, the term "PNA (Peptide Nucleic Acid)" refers to an artificially synthesized polymer similar to DNA or RNA, which was first introduced in 1991 by Professors Nielsen, Egholm, Berg and Buchardt of the University of Copenhagen, Denmark. While DNA has a phosphate-ribose sugar backbone, PNA has a repeating N-(2-aminoethyl)-glycine backbone linked by peptide bonds, which greatly increases the binding strength and stability to DNA or RNA, and is used in molecular biology, diagnostic analysis and antisense therapy. PNA is disclosed in detail in the literature [Nielsen PE, Egholm M, Berg RH, Buchardt O (December 1991). "Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide". Science 254 (5037): 1497-1500].

[0055] In the present invention, the "aptamer" is an oligonucleic acid or peptide molecule, and the general content of aptamers is disclosed in detail in the literature [Bock LC et al., Nature 355(6360):5646(1992); Hoppe-Seyler F, Butz K "Peptide aptamers: powerful new tools for molecular medicine". J Mol Med. 78(8):42630(2000); Cohen BA, Colas P, Brent R. "An artificial cell-cycle inhibitor isolated from a combinatorial library". Proc Natl Acad Sci USA. 95(24):142727(1998)].

[0056] In the present invention, the first binding portion may include, but is not limited to, one or more compounds selected from the group consisting of the following chemical formulas 1 to 5, which can non-specifically bind to the analyte.

[0057] [ka]

[0058] [ka]

[0059] [ka]

[0060] [ka]

[0061] [ka]

[0062] In the above Chemical Formulas 1 to 5, p is an integer from 7 to 20. * indicates [M] n Or the above L 1 This is the site that is linked to

[0063] In the first binding portion of the present invention, the compound represented by Chemical Formula 1, 2 or 4 binds the analyte and copper ions (Cu 2+ ), zinc ion (Zn 2+ ) or cobalt ion (Co 2+ ) can be indirectly linked.

[0064] In the present invention, any one of the residues of M constituting the polymer represented by formula 2 is linked to the first binding portion directly or via a linker.

[0065] In the present invention, the "linker" refers to a compound that cross-links with another compound, and may be a chemical bond such as a covalent bond or a physical bond such as an ionic bond. A protective group may be introduced during the cross-linking process.

[0066] In the present invention, the linker may include any one or more selected from the following chemical formulas 6 to 8, and includes, without limitation, any linker used in small molecule drug conjugate (SMDC) technology such as antibody-drug conjugates (ADC) or ligand-drug conjugates (LDC).

[0067] [ka]

[0068] [ka]

[0069] [ka]

[0070] In the above Chemical Formulae 6 to 8, q is an integer from 1 to 5; * indicates [M] n Or the above L 1 and the part where the connection is made.

[0071] In the present invention, "small molecule drug conjugates (SMDCs)" are a technology used for drug delivery, which is composed of three modules: a targeting means such as a ligand or antibody, a linker, and a drug-loaded module.

[0072] In the present invention, in the complex compound represented by the formula 1, the [M] n and the above L 1 or between the linker of L 1 The linker and the N 1 A spacer may further be included between the first coupling portion and the second coupling portion.

[0073] In the present invention, the "spacer" is also called a stretcher, which connects the first binding portion, the linker, or the polymer, secures a space between the first binding portion and the polymer, and may be cleaved by a catalyst or may be an amino acid or an oligopeptide, but is not limited thereto.

[0074] In the present invention, the complex compound represented by the formula 1 may be one represented by any one of the following chemical formulae 9 to 13, but is not limited thereto.

[0075] [ka] [ka]

[0076] [ka]

[0077] [ka]

[0078] [ka]

[0079] In the above Chemical Formulas 9 to 13, The definitions for n and M are as defined in Formula 1 above.

[0080] In the present invention, the composition for detecting or measuring the analyte may contain one kind of conjugate compound represented by formula 1, but may contain two or more different kinds of conjugate compounds represented by formula 1. In this case, the different conjugate compounds may be different in at least one of their internal polymer, linker, and first binding portion. In particular, the "(X 1 X 2 …X m )" may be different from each other, or the polymerization number of M, that is, n in the formula 1 may be different.

[0081] In addition, in the present invention, the composition for detecting or measuring the analyte comprises two or more compositions each containing a different complex compound represented by formula 1. In this case, there is an advantage that analysis of multiple analytes, multiple individuals, or multiple samples can be performed in a single analysis by using different complex compounds for multiple analytes, using compositions containing different complex compounds for samples obtained from multiple individuals, or using compositions containing different complex compounds for multiple samples obtained from one individual.

[0082] Another embodiment of the present invention relates to a kit for detecting or measuring an analyte, comprising a composition for detecting or measuring an analyte according to the present invention.

[0083] In the present invention, the kit may be, but is not limited to, a protein chip kit, a rapid kit, or an MRM (Multiple reaction monitoring) kit.

[0084] In the present invention, the kit may further comprise one or more other components, solutions or devices suitable for the analytical method, such as a second binding moiety, an immobilizer, a carrier, biotin, a washing solution or a reaction solution.

[0085] In the present invention, the kit may further comprise a second binding moiety that specifically binds to the analyte, has high affinity for the analyte, and has little cross-reactivity with other biomarkers.

[0086] In the present invention, the second binding portion may include, but is not limited to, one or more selected from the group consisting of a probe, an antisense nucleotide, an antibody, an oligopeptide, a ligand, a PNA (peptide nucleic acid), and an aptamer that specifically binds to the analyte.

[0087] In addition, in the present invention, the second binding moiety may include two or more different types. In particular, when the composition for detecting or measuring the analyte includes two or more different types of complex compounds represented by Formula 1, the composition may include two or more different types of second binding moieties such that different second binding moieties correspond to each complex compound.

[0088] Furthermore, in the present invention, the second binding portion can bind to an immobilized body, a carrier, or biotin.

[0089] In the present invention, the material of the immobilizer may be any one or more selected from nitrocellulose, PVDF, polyvinyl resin, polystyrene resin, glass, silicone, and metal, and the shape of the immobilizer may be a membrane, a substrate, a plate, a well plate, a multi-well plate, a filter, a cartridge, a column, or a porous body, but any shape that can immobilize the second binding portion two-dimensionally is included without limitation.

[0090] In the present invention, the carrier may be any material that has a three-dimensional structure and can three-dimensionally fix the second binding portion, and is preferably a material that can be easily separated or collected by weight, charge, or magnetism, for example, but is not limited to, magnetic particles. In the present invention, the type of the magnetic particles is not particularly limited, and the magnetic particles may be one or more materials selected from the group consisting of iron, cobalt, nickel, and oxides or alloys thereof, and for example, iron oxide (Fe 2 O 3 , Fe 3 O 4 ), ferrite (Fe 3 O 4 In the case of CoFe, one of the Fe atoms has been changed to another magnetically relevant atom. 2 O 4 , MnFe 2 O 4 ) and / or alloys (alloyed with noble metals to improve the oxidation problem, conductivity and stability caused by magnetic atoms, e.g. FePt, CoPt, etc.), etc., specific examples include maghemite (γ-Fe 2 O 3 ), magnetite (Fe 3 O 4 ), cobalt ferrite (CoFe 2 O 4 ), manganese ferrite (MnFe 2 O 4), iron platinum alloy (FePt alloy), iron cobalt alloy (FeCo alloy), cobalt nickel alloy (CoNi alloy) or cobalt platinum alloy (CoPt alloy), but is not limited thereto.

[0091] In the present invention, the biotin can be bound to a streptavidin or avidin protein bound to an immobilized body or carrier.

[0092] In the present invention, the washing solution may contain a phosphate buffer solution, NaCl or a non-ionic surfactant, and may preferably be, but is not limited to, a buffer solution (PBST) consisting of 0.02 M phosphate buffer solution, 0.13 M NaCl and 0.05% Tween 20. The non-ionic surfactant may be selected from the group consisting of Digitoninum, Triton X-100, Triton X-114, Tween-20 and Tween-80, but is not limited thereto.

[0093] In the present invention, the reaction solution contains CuCl 2 , Cu(NO 3 ) 2 , CoCl 2 , Co(NO 3 ) 2 , Zn(NO 3 ) 2 and ZnCl 2 The metal salt may include one or more metal salts selected from the group consisting of, but is not limited to, the metal salt.

[0094] In one embodiment of the present invention, when the second binding part is a capture antibody, after an antigen-antibody binding reaction between the second binding part and the analyte, the immobilizer may be washed 3 to 6 times by adding the washing solution. Here, the reaction stop solution is a sulfuric acid solution (H 2 SO 4The washing solution may preferably be one or more non-ionic surfactants selected from Digitoninum, Triton X-100, Triton X-114, Tween-20, and Tween-80, but is not limited thereto.

[0095] According to yet another embodiment of the present invention, there is provided a method for analyzing an analyte, comprising a reaction step of reacting the analyte with a composition for detecting or measuring the analyte of the present invention, and a detection step of detecting or measuring M in a complex compound of the composition.

[0096] In the present invention, the analyte is present in a biological sample isolated from a target individual, and includes, for example, any one or more selected from the group consisting of proteins, lipoproteins, glycoproteins, DNA, and RNA, but is not limited to, any molecule in the body that contains organic substances such as amino acids, nucleotides, monosaccharides, or lipids as monomers.

[0097] In the present invention, the "individual" may be an individual that contains or is expected to contain the analyte in the biological sample. If the analyte present in a small amount in the biological sample can be analyzed, it can be applied to early diagnosis, prognosis prediction, and reactivity to drugs for various diseases.

[0098] In the present invention, the "biological sample" refers to any substance, biological fluid, tissue, or cell obtained from or derived from an individual, and includes, for example, whole blood, leukocytes, peripheral blood mononuclear cells, buffy coat, plasma, serum, sputum, tears, mucus, nasal washes, nasal aspirate, breath, urine, semen, saliva, peritoneal washings, ascites, cystic fluid, meningeal fluid, amniotic fluid, glandular fluid, pancreatic fluid, lymphatic fluid, and the like. The fluid may include, for example, whole blood, plasma or serum, but may be, for example, whole blood, plasma, pleural fluid, nipple aspirate, bronchial aspirate, synovial fluid, joint aspirate, organ secretions, cells, cell extracts or cerebrospinal fluid.

[0099] In the present invention, before the reaction step, an immobilization step of immobilizing the analyte by contacting the analyte with a second binding moiety can be carried out first.

[0100] In the present invention, the second binding portion may include one or more selected from the group consisting of a probe, an antisense nucleotide, an antibody, an oligopeptide, a ligand, a PNA (peptide nucleic acid), and an aptamer that specifically binds to the analyte, but is not limited thereto.

[0101] In the present invention, the second binding portion may bind to an immobilized body, a carrier, or biotin to form a second binding portion-immobilized body complex or a second binding portion-carrier complex.

[0102] In the present invention, the material of the immobilizer may be any one or more selected from nitrocellulose, PVDF, polyvinyl resin, polystyrene resin, glass, silicone, and metal, and the shape of the immobilizer may be a membrane, a substrate, a plate, a well plate, a multi-well plate, a filter, a cartridge, a column, or a porous body, but any shape that can immobilize the second binding portion two-dimensionally is included without limitation.

[0103] In the present invention, the carrier may be any material that has a three-dimensional structure and can three-dimensionally fix the second binding portion, and is preferably a material that can be easily separated or collected by weight, charge, or magnetism, for example, but is not limited to, magnetic particles. In the present invention, the type of the magnetic particles is not particularly limited, and the magnetic particles may be one or more materials selected from the group consisting of iron, cobalt, nickel, and oxides or alloys thereof, and for example, iron oxide (Fe 2 O 3 , Fe 3 O 4 ), ferrite (Fe 3 O 4 In the case of CoFe, one of the Fe atoms has been changed to another magnetically relevant atom. 2 O 4 , MnFe 2 O 4 ) and / or alloys (alloyed with noble metals to improve the oxidation problem, conductivity and stability caused by magnetic atoms, e.g. FePt, CoPt, etc.), etc., specific examples include maghemite (γ-Fe 2 O 3 ), magnetite (Fe3 O 4 ), cobalt ferrite (CoFe 2 O 4 ), manganese ferrite (MnFe 2 O 4 ), iron platinum alloy (FePt alloy), iron cobalt alloy (FeCo alloy), cobalt nickel alloy (CoNi alloy) or cobalt platinum alloy (CoPt alloy), but is not limited thereto.

[0104] In the present invention, the biotin binds to streptavidin or avidin protein bound to an immobilizer or carrier to form a second binding portion-immobilizer complex or a second binding portion-carrier complex.

[0105] In the present invention, if necessary, following the immobilization step, a first separation step of separating the analyte-second binding moiety complex, the analyte-second binding moiety-immobilizer complex, or the analyte-second binding moiety-carrier complex formed by immobilization of the analyte may be further included.

[0106] In the present invention, during the first separation step, the analyte-second binding moiety complex, analyte-second binding moiety-immobilized body complex or analyte-second binding moiety-carrier complex can be separated by weight, charge or magnetism depending on the attributes of the second binding moiety or the immobilized body, carrier or biotin to which the second binding moiety binds.

[0107] In the present invention, if necessary, following the first separation step, a first washing step of washing the analyte-second binding moiety complex, the analyte-second binding moiety-immobilized body complex or the analyte-second binding moiety-carrier complex with a washing solution may be further included.

[0108] In the present invention, the first washing step can remove substances that have not formed complexes and are not fixed in the biological sample.

[0109] In the present invention, the washing solution used in the first washing step may contain a phosphate buffer solution, NaCl or a non-ionic surfactant, and may be, but is not limited to, a buffer solution (PBST) consisting of 0.02 M phosphate buffer solution, 0.13 M NaCl and 0.05% Tween 20. The non-ionic surfactant may be selected from the group consisting of Digitoninum, Triton X-100, Triton X-114, Tween-20 and Tween-80, but is not limited to this.

[0110] In the present invention, after the first washing step, a reaction step can be carried out in which the analyte is reacted with a composition for detecting or measuring the analyte of the present invention.

[0111] In the present invention, the composition for detecting or measuring the analyte of the present invention used in the reaction step may contain one kind of conjugate compound represented by formula 1, or may contain two or more different kinds of conjugate compounds represented by formula 1. In this case, at least one of M, linker and first binding portion in each conjugate compound may be different, and in particular, "(X 1 X 2 …X m )" may be different from each other, or the polymerization number of M, i.e., the number n in the above formula 1, may be different. In such cases, there is an advantage that a single analysis can be performed on a plurality of analytes, a plurality of individuals, or a plurality of samples, by using different complex compounds for each of the plurality of analytes, a different complex compound for each of the samples obtained from a single individual, or a different complex compound for each of the samples obtained from a single individual.

[0112] In the present invention, a metal salt may be additionally added during the reaction step, so that the first binding portion may indirectly bind to the analyte via a metal ion of the metal salt, and preferably, the analyte may be treated with a metal salt prior to treatment with the composition of the present invention.

[0113] In the present invention, the metal salt is CuCl 2 , Cu(NO 3 ) 2 , CoCl 2 , Co(NO 3 ) 2 , Zn(NO 3 ) 2 and ZnCl 2 The compound may be one or more selected from the group consisting of, but is not limited to, the compound.

[0114] In the present invention, the reaction step results in the formation of [M] n -L 1 -N 1 - the analyte complex, [M] n -L 1 -N 1 -analyte-second binding site complex, [M] n -L 1 -N 1 - the analyte-second binding moiety-immobilized complex or [M] n -L 1 -N 1 The method may further comprise a second separation step for separating the analyte-second binding moiety-support complex.

[0115] In the present invention, in the second separation step, the [M] is selected depending on the attribute of the second binding portion, or the immobilized body, carrier, or biotin to which the second binding portion is bound. n -L 1 -N 1 - the analyte-second binding moiety-immobilized complex or [M] n -L 1 -N 1 The analyte-second binding moiety-support complex can be separated gravimetrically, electrically or magnetically.

[0116] In the present invention, if necessary, following the second separation step, [M] n -L 1 -N 1 -analyte-second binding site complex, [M] n -L 1 -N 1 - the analyte-second binding moiety-immobilized complex or [M] n -L 1 -N 1 The method may further include a second washing step of washing the analyte-second binding portion-carrier complex with a washing solution.

[0117] In the present invention, the second washing step can remove substances that have not formed a complex and are not immobilized in the reaction composition.

[0118] In the present invention, the washing solution used in the second washing step may contain a phosphate buffer solution, NaCl or a non-ionic surfactant, and may be, but is not limited to, a buffer solution (PBST) consisting of 0.02 M phosphate buffer solution, 0.13 M NaCl and 0.05% Tween 20. The non-ionic surfactant may be selected from the group consisting of Digitoninum, Triton X-100, Triton X-114, Tween-20 and Tween-80, but is not limited to this.

[0119] In the present invention, the [M] n -L 1 -N 1 - the analyte complex, [M] n -L 1 -N 1 -analyte-second binding site complex, [M] n -L 1 -N 1 - the analyte-second binding moiety-immobilized complex or [M] n -L 1 -N 1The method may further comprise a cleavage step of cleaving the M unit from the analyte-second binding moiety-support complex.

[0120] The cleavage step of the present invention is carried out by a catalyst that specifically cleaves the bond between the adjacently linked M and M, and in this case, the catalyst may be an enzyme or a synthetic catalyst.

[0121] In the present invention, the enzyme may be, but is not limited to, a peptide hydrolase, preferably a peptide endohydrolase, or a lactase.

[0122] In the present invention, the peptide hydrolase can be used to specifically hydrolyze only peptide bonds between specific amino acids.

[0123] In the present invention, the peptide hydrolase may be one or more selected from the group consisting of trypsin, chymotrypsin, thrombin, plasmin, subtilisin, thermolysin, pepsin, and glutamyl endopeptidase, and preferably one or more selected from the group consisting of trypsin, chymotrypsin, subtilisin, thermolysin, and glutamyl endopeptidase, but is not limited thereto.

[0124] In the present invention, the synthetic catalyst enables an efficient cleavage reaction without being restricted by conditions such as pH and temperature.

[0125] In the present invention, the synthetic catalyst may be, but is not limited to, an artificial metalloenzyme, an organic artificial enzyme, or a reducing agent that breaks disulfide bonds.

[0126] In the present invention, the artificial metalloproteases include, but are not limited to, water-soluble catalysts using copper (II), cobalt (III), iron (III), palladium (II), cerium (IV), etc. as the catalyst center, or copper (II) complex compounds attached to a support.

[0127] In the present invention, the organic artificial proteases may be those having functional groups attached to a silica support or a polystyrene support, but are not limited thereto.

[0128] In the present invention, the reducing agent that cleaves the disulfide bond may be glutathione, thioglycolic acid, or cysteamine, but includes, without limitation, any agent that can reduce the disulfide bond between M and M to a thiol group.

[0129] In the present invention, after the cleavage step, a detection step of detecting or measuring the cleaved M can be carried out.

[0130] In the present invention, when the M is a peptide, in the detection step, if necessary, "[M] n " can be subjected to a cleavage and fragmentation process to quantify n peptide fragments each having a unit M, and in this case, the quantitative sensitivity can be improved by n times compared to the quantification of the peptide polymer itself.

[0131] In the present invention, when M is a monosaccharide, an oligosaccharide, or a polysaccharide, in the detection step, if necessary, "[M] n " can be cleaved and fragmented with lactase or under acidic conditions to quantify n units of monosaccharides, oligosaccharides or polysaccharides, each of which is a unit M. In this case, the quantitative sensitivity can be improved by n times compared to quantifying the polymer.

[0132] In the present invention, the detection, quantification or comparative analysis method of M in the detection step may include, but is not limited to, one or more selected from the group consisting of protein chip analysis, immunoassay, ligand binding assay, MALDI-TOF (Matrix Assisted Laser Desorption / Ionization Time of Flight Mass Spectrometry) analysis, SELDI-TOF (Sulface Enhanced Laser Desorption / Ionization Time of Flight Mass Spectrometry) analysis, radioimmunoassay, radial immunodiffusion, Ouchterlony immunodiffusion, rocket immunoelectrophoresis, tissue immunostaining, complement fixation analysis, two-dimensional electrophoresis analysis, liquid chromatography-mass spectrometry (LC-MS), LC-MS / MS (liquid chromatography-tandem Mass Spectrometry), Western blotting and multiple reaction monitoring (MRM).

[0133] In the present invention, the multiple reaction monitoring method is carried out using a mass spectrometer, preferably a triple quadrupole mass spectrometer.

[0134] In the present invention, the multiple reaction monitoring (MRM) method using a mass spectrometer is an analytical technique that can selectively separate, detect, and quantify a specific analyte, and monitor its concentration change. MRM is a method that can quantitatively and accurately perform multiple measurements of substances such as trace biomarkers present in a biological sample, and selectively transmits parent ions from ion fragments generated from an ionization source to a collision tube using a first mass filter (Q1). The parent ions that reach the collision tube then collide with the internal collision gas, break up, generate child ions, and are sent to a second mass filter (Q2), where only the characteristic ions are transmitted to a detection section. This method is an analytical method with high selectivity and sensitivity that can detect only information on the target component. The MRM method has the advantages of being easy to measure multiple small molecules simultaneously, not requiring antibodies, and being able to confirm the relative concentration difference of protein diagnostic marker candidates between normal people and patients. In addition, due to its excellent sensitivity and selectivity, MRM analytical methods have been introduced for the analysis of complex proteins and peptides in blood, especially in proteomic analysis using mass spectrometry (Anderson L. et al., Mol Cell Proteomics, 5:375-88, 2006; DeSouza, LV et al., Anal. Chem., 81:3462-70, 2009).

[0135] In the method of the present invention, instead of the complex proteins in the blood as the analyte, the "[M] n " or n M units cleaved therefrom, can be analyzed using the MRM method, which not only has a significant effect on the speed, ease, and accuracy of analysis, but also allows the analysis of multiple biological samples or multiple analytes to proceed simultaneously.

[0136] FIG. 1 is a schematic diagram illustrating a method for analyzing an analyte according to one embodiment of the present invention, in which 1) the second binding portion is brought into contact with the analyte, and then the analyte is immobilized using a column such as a reverse phase column / ion exchange column, 2) impurities are removed by washing, 3) a complex of a repeatable peptide fragment, which is an amplification tag, and a first binding portion capable of non-specifically binding to the analyte is reacted with the immobilized analyte, and 4) the peptide repeats contained in the complex are cleaved into unit fragments by an enzyme, and the analyte can be quantitatively analyzed with high sensitivity by mass spectrometry due to the amplification effect caused by the repetition of substances with the same mass / charge ratio.

[0137] FIG. 2 is a schematic diagram illustrating a method for analyzing an analyte according to one embodiment of the present invention, in which 1) the analyte is contacted with a second binding moiety linked to magnetic particles, and then the magnetic force is adjusted to immobilize the analyte, 2) impurities are removed by washing, 3) a complex of a repeatable peptide fragment, which is an amplification tag, and a first binding moiety that can non-specifically bind to the analyte is reacted with the immobilized analyte, and 4) the peptide repeats contained in the complex are cleaved into unit fragments by an enzyme, and the analyte can be quantitatively analyzed with high sensitivity by mass spectrometry due to the amplification effect caused by the repetition of substances with the same mass / charge ratio.

[0138] 3 is a schematic diagram showing an analytical method for an analyte according to an embodiment of the present invention, in which 1) the analyte is contacted with a second binding moiety linked to biotin, and then the analyte is immobilized by reacting with an immobilizer (container) having streptavidin immobilized thereon, 2) impurities are removed by washing, 3) a complex of a repeatable peptide fragment, which is an amplification tag, and a first binding moiety capable of non-specifically binding to the analyte is reacted with the immobilized analyte, and 4) the peptide repeats contained in the complex are cleaved into unit fragments by an enzyme, and the analyte can be quantitatively analyzed with high sensitivity by the amplification effect due to the repetition of substances with the same mass / charge ratio by mass spectrometry.

[0139] According to yet another aspect of the present invention, the present invention provides a method for diagnosing the presence or absence of a disease in a subject, using a composition for detecting or measuring an analyte by mass spectrometry of the present invention; or a detection kit including the composition for detecting or measuring an analyte of the present invention.

[0140] According to a specific embodiment of the invention, the diagnostic method of the invention comprises the steps of: A reaction step of reacting an analyte with a composition for detecting or measuring an analyte, which comprises a complex compound represented by formula 1 of the present invention, or a detection kit comprising the composition for detecting or measuring an analyte of the present invention; A detection step for detecting or measuring the repeatable unit compound (M) of the present invention present in the complex compound contained in the composition or kit.

[0141] According to a particular embodiment of the invention, the analyte is the blood of a diagnostic subject, more particularly, the analyte is a peptide present in the blood of a diagnostic subject.

[0142] According to a particular embodiment of the invention, the disease that can be diagnosed by the diagnostic method of the invention is cancer.

[0143] The detection or measurement composition, detection kit and detection step of the present invention have already been described above, so they will be omitted to avoid excessive duplication. Effect of the Invention

[0144] According to the present invention, it is possible to quantitatively analyze an analyte with excellent selectivity and sensitivity, and to achieve the effect of amplification.Furthermore, it is possible to simultaneously process various analytes and a large amount of samples, and it has excellent analytical efficiency and performance.

[0145] In addition, according to the present invention, when detecting various analytes from a sample, the residence time can be controlled, and the analysis time can be adjusted or the residence time between samples can be appropriately allocated to increase the ease of analysis. [Brief description of the drawings]

[0146] [Figure 1] FIG. 1 is a schematic diagram illustrating a method for analyzing an analyte according to an embodiment of the present invention. [Diagram 2] FIG. 1 is a schematic diagram illustrating a method for analyzing an analyte according to an embodiment of the present invention. [Diagram 3] FIG. 1 is a schematic diagram illustrating a method for analyzing an analyte according to an embodiment of the present invention. [Figure 4] 1A to 1C are diagrams showing a process for manufacturing a detection sensor according to an embodiment of the present invention in Preparation Example 1. [Diagram 5] FIG. 1 is a diagram confirming coupling by a Kaiser test according to an embodiment of the present invention in Preparation Example 1. [Figure 6] 10A to 10C are diagrams illustrating a process for manufacturing a detection sensor according to an embodiment of the present invention in a preparation example 2. [Figure 7] 11A to 11C are diagrams illustrating a process for manufacturing a detection sensor according to an embodiment of the present invention in a preparation example 3. [Figure 8] FIG. 13 shows an aptamer-MNP complex according to an embodiment of the present invention in Preparation Example 4. [Figure 9] FIG. 13 is a diagram showing a process for producing an aptamer-MNP complex according to an embodiment of the present invention in Preparation Example 4. [Figure 10] FIG. 13 shows the results of mass spectrometry of a peptide module prepared according to an embodiment of the present invention in Preparation Example 6. [Figure 11] FIG. 13 shows the results of mass spectrometry of a peptide module prepared according to an embodiment of the present invention in Preparation Example 6. [Figure 12] FIG. 13 is a diagram showing a unit body according to an embodiment of the present invention in Preparation Example 7. [Figure 13] FIG. 13 is a diagram showing M according to an embodiment of the present invention in preparation example 7. [Figure 14] FIG. 13 is a diagram showing M according to an embodiment of the present invention and a unit body obtained by cutting it in Preparation Example 8. [Figure 15] FIG. 2 shows the results of mass spectrometry of peptides prepared according to examples of the present invention in Experimental Example 1. [Figure 16] FIG. 11 is a diagram confirming the amplification effect of a peptide according to an embodiment of the present invention in Experimental Example 2. [Figure 17] FIG. 11 is a diagram confirming the amplification effect of a peptide according to an embodiment of the present invention in Experimental Example 2. [Figure 18] FIG. 11 is a diagram confirming the effect of improving detection sensitivity during mass spectrometry by peptide amplification according to an embodiment of the present invention in Experimental Example 2. [Figure 19A] In Experimental Example 3, the effect of improving the detection sensitivity during mass spectrometry by amplifying peptides according to an embodiment of the present invention is shown, when the amplification is repeated a small number of times. [Figure 19B] In Experimental Example 3, the effect of improving the detection sensitivity during mass spectrometry by amplifying peptides according to an embodiment of the present invention is shown by the results confirmed when the amplification was repeated many times (for example, 100 times or more). [Figure 20] FIG. 13 is a diagram showing a quantification method according to an embodiment of the present invention in Experimental Example 4. [Figure 21] FIG. 11 is a diagram showing a magnetic field processing method according to an embodiment of the present invention in Experimental Example 4. [Figure 22] FIG. 13 is a diagram showing a complex of [M]n-L1-N1-analyte-second binding portion-carrier according to an embodiment of the present invention in Experimental Example 4. [Figure 23] FIG. 13 is a diagram showing the results of quantifying the expression levels of proteins 1 to 4 according to an embodiment of the present invention in Experimental Example 5. [Figure 24] FIG. 1 shows the structure of a complex compound according to an embodiment of the present invention in Experimental Example 6. [Diagram 25] FIG. 13 is a diagram showing a method for performing mass spectrometry after cleavage of an SLVPR fragment in a complex compound according to an embodiment of the present invention in Experimental Example 6. [Figure 26] FIG. 13 is a diagram showing a method for performing fluorescence analysis using a complex compound according to an embodiment of the present invention in Experimental Example 6. [Figure 27] FIG. 11 is a graph showing the change in sensitivity depending on the concentration of an analyte in mass spectrometry performed using a complex compound according to an embodiment of the present invention in Experimental Example 6. [Figure 28]FIG. 11 is a graph showing the change in sensitivity depending on the concentration of the analyte during fluorescence analysis using the complex compound according to an embodiment of the present invention in Experimental Example 7. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0147] The present invention will be described in detail with reference to the following examples. However, the following examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following examples.

[0148] Working Example The meanings of the abbreviations used in the following examples of the present invention are shown in Table 1 below.

[0149] [Table 1]

[0150] [Preparation Example 1] Preparation of a detection sensor for chemical formula 9 The synthesis process of a polymer (substitute peptide) used to synthesize a conjugate compound represented by the following formula 9 of the present invention and the process of linking the polymer to a first binding moiety are shown in FIG.

[0151] [ka]

[0152] As shown in Figure 4, for solid-phase peptide synthesis, Fmoc-AA-OH, HOBt, and DIC were dissolved in DMF using EDCI synthesis with Wang resin, and added to the reaction vessel and stirred. Capping of the unreacted sites of the resin was performed using AC2O. Deprotection of Fmoc was performed with piperidine. Similarly, Fmoc-AA-OH, HOBt, and DIC were dissolved in DMF, and added to the reaction vessel and stirred. Thereafter, the completion of coupling was monitored by Kaiser test as shown in Figure 5. The remaining amino acid couplings in the sequence were performed using DIC / HOBt. The peptidyl resin was dried and taken for total cleavage. The peptidyl resin was treated with TFA at room temperature. After filtration, the filtrate was solid-separated using MTBE.

[0153] [Preparation Example 2] Preparation of a detection sensor for chemical formula 10 A process for synthesizing the detection sensor complex compound represented by the following Formula 10 of the present invention is shown in FIG.

[0154] [ka]

[0155] [ka]

[0156] As shown in FIG. 6, chloroacetic acid was added to the * site of Chemical Formula 2, and then a peptide polymer was linked as shown in Chemical Formula 10.

[0157] [Preparation Example 3] Preparation of detection sensor for chemical formula 11 A process for synthesizing the detection sensor complex compound represented by the following Formula 11 of the present invention is shown in FIG.

[0158] [ka]

[0159] As shown in Figure 7, the Wang resin was placed in a solid-phase peptide synthesis vessel for solid-phase peptide synthesis. HNA was dissolved in DMF, and HOBt, DIC were dissolved in DMF using EDCI synthesis, added to the reaction vessel and stirred. Capping of the unreacted sites of the resin was performed using AC2O. Deprotection of Fmoc was performed with piperidine. Similarly, Fmoc-AA-OH, HOBt, and DIC were dissolved in DMF, added to the reaction vessel and stirred. The rest of the amino acid coupling in the sequence was performed using DIC / HOBt. The peptidyl resin was dried and taken for total cleavage. The peptidyl resin was treated with TFA at room temperature. After filtration, the filtrate was solid-separated using MTBE.

[0160] [Preparation Example 4] Preparation of aptamer-MNP complex The process for preparing an aptamer-MNP complex (second binding portion-carrier complex) as shown in FIG. 8 is shown in FIG.

[0161] As shown in Figure 9, FeCl 2 .4H 2 O and FeCl 3 .6H 2 O was washed in water by repeatedly heating and cooling, and then dried. MNP was dispersed using an ultrasonic disintegrator. APTES was slowly added to MNP, reacted, and dried in a vacuum oven. Completion of coupling was monitored using the Kaiser test. Chloroacetic acid was added to the compound, reacted, and dried in a vacuum oven. Then, the aptamer was linked.

[0162] [Preparation Example 5] Preparation of peptide represented by M and confirmation of residence time (1) In order to confirm the simultaneous detection capability of the detection sensor of the present invention, the retention time (RT) according to the peptide sequence represented by M was measured, and the results are shown in Tables 2-20.

[0163] [Table 2]

[0164]

Table 3

[0165]

Table 4

[0166]

Table 5

[0167]

Table 6

[0168]

Table 7

[0169]

Table 8

[0170]

Table 9

[0171]

Table 10

[0172]

Table 11-1

[0173]

Table 11-2

[0174]

Table 12-1

[0175]

Table 12-2

[0176]

Table 13-1

[0177]

Table 13-2

[0178]

Table 14-1

[0179]

Table 14-2

[0180]

Table 15-1

[0181]

Table 15-2

[0182] [Table 16]

[0183] [Table 17]

[0184] [Table 18-1]

[0185] [Table 18-2]

[0186] [Table 19]

[0187] As shown in Tables 2 to 19, after preparing a peptide represented by M, the residence time (RT) according to the sequence was measured, and as a result, various sequences could be prepared for each residence time (RT).

[0188] [Table 20]

[0189] In addition, as shown in Table 20, after preparing additional peptides represented by M, the hydrophobicity and retention time (RT) according to the sequence were measured, and various sequences with retention times (RT) of 30 seconds to 20 minutes were prepared. When the same biomarker is to be quantified in multiple samples using this, a binding part that recognizes an analyte, such as a detection part composed of a different sequence for each sample, can be configured, and multiple samples can be pooled together and simultaneously quantified.

[0190] [Preparation Example 6] Preparation of peptide represented by M and confirmation of residence time (2) As in Preparation Example 5, in order to confirm the simultaneous detection capability of the detection sensor of the present invention, the peptide (TLVPR) represented by SEQ ID NO: 688 and the peptide (SLVPR) represented by SEQ ID NO: 689 were synthesized, and the retention time (RT) according to the sequence of such peptides was measured, and the results are shown in Table 21. In addition, these compounds were prepared at a concentration of 1.5 ug / ml, and the peak intensity of the peptide fragments was confirmed by the mass / charge ratio of each peptide fragment using a mass spectrometer, and the results are shown in Figures 10 and 11.

[0191] [Table 21]

[0192] [Preparation Example 7] Synthesis of Units and M (1) In the formula 2 of the present invention, each X 1 ~X m Exemplary types of amino acids or amino acid analogs that can correspond to are shown in Figure 12. Examples of M obtained by polymerizing these amino acids or amino acid analogs are shown in Figure 13.

[0193] [Preparation Example 8] Synthesis of Units and M (2) As shown in Figure 14, a disaccharide that can be M of the present invention was prepared. The M was decomposed into two monosaccharides, which are mutual isomers, under acidic conditions or with lactase, and the sensitivity was increased by two times when the result of mass spectrometry was performed.

[0194] [Experimental Example 1] Simultaneous detection experiment for four peptides represented by M In order to confirm the ability of the present invention to simultaneously detect peptides represented by M, the results of detecting peptides having the sequences in Table 22 below by mass spectrometry MRM are shown in FIG.

[0195] [Table 22]

[0196] As shown in FIG. 15, it was confirmed that peptides having the four sequences shown in Table 22 above could be simultaneously detected.

[0197] [Experimental Example 2] Confirmation of sensitivity to peptide represented by M (1) In order to confirm the amplification effect due to the repetition of the peptide sequence of the present invention, the peptide (LTLK) of sequence number 652 in Table 20 and a polymer in which the peptide is repeated twice (LTLKLTLK) were treated with trypsin, and the peak magnitudes were measured using a mass spectrometer. The results are shown in Figures 16 and 17. The sensitivity (CPS) of the mass spectrometer according to the number of polymerizations (n ​​number) was calculated, and the results are shown in Figure 18.

[0198] As shown in Figures 16 and 17, the peak of the polymer (LTLKLTLK) in which the peptide is repeated twice was twice as large as the peak of the peptide (LTLK) of SEQ ID NO: 652. In addition, as shown in Figure 18, when the peptide is repeated twice, the sensitivity is exactly two times higher, confirming that the sensitivity increases according to the number of polymerizations when the peptide is polymerized.

[0199] [Experimental Example 3] Confirmation of sensitivity to peptide represented by M (2) In order to confirm the amplification effect by repeating the peptide sequence of the present invention, a peptide fragment (FLK) of SEQ ID NO: 690 or a peptide in which such a fragment is repeated 2 times, 4 times, or 6 times was prepared, and then such a compound was prepared at a concentration of 1 pM, trypsin was added in an amount of 1:20 to 100 (w / w) relative to the compound, and the compound was fragmented into FLK fragments at 37 ° C. After completely drying and resuspension, the mass / charge ratio of the FLK peptide fragment was input using a mass analyzer (MRM mode), the area of ​​the chromatogram was calculated, and the change in peak intensity due to the polymerization number of the peptide fragment was measured, and the results are shown in Figure 19A.

[0200] As shown in FIG. 19A, when the peptide fragment represented by FLK of SEQ ID NO: 690 was polymerized and repeated, it was confirmed that the detection sensitivity increased in proportion to the number of polymerized fragments.

[0201] In addition, in order to measure the degree of increase in detection sensitivity when the peptide sequence of the present invention is repeated 100 times or more, a peptide in which a fragment consisting of the FTPVR sequence is repeated 120 times was prepared, and the change in peak intensity was measured in the same manner as described above. As a result, as shown in Figure 19B, the 120-repeated polymer showed an amplification factor of about 136 times compared to the FTPVR monomer, and it was found that the detection target peptide of the present invention shows a detection sensitivity that increases almost linearly or more proportionally to the number of polymerizations.

[0202] [Experimental Example 4] Confirmation of diagnostic capabilities using detection sensors (1) In order to confirm the diagnostic ability of the detection sensor of the present invention, a protein detection experiment was carried out as shown in FIG. 20. First, a target protein for cancer diagnosis was selected, and then an aptamer specific to the target protein was prepared, and an aptamer-MNP complex was prepared in the same manner as in Preparation Example 4. Thereafter, the prepared aptamer-MNP complex was placed in a separate well, and human blood requiring diagnosis was treated in each well for reaction. After the reaction was completed, a magnetic field was applied to each well, and a photograph of the blood after treatment is shown in FIG. 21.

[0203] As shown in Figure 21, impurities other than the target protein that specifically binds to each aptamer were removed in each well. 2 Reaction with each protein 1-4 and residual CuCl 2 The treatment of each well with the complex compound represented by formula 10 and the removal of the remaining complex compound are sequentially performed to obtain [M] as shown in FIG. n -L 1 -N 1 Only the analyte-second binding portion-carrier complex was left in the well. Then, the well was treated with trypsin and filtered to obtain peptides.

[0204] [Experimental Example 5] Confirmation of diagnostic capabilities using detection sensors (2) - Simultaneous measurement of multiple samples In order to confirm the diagnostic capability of the detection sensor of the present invention, simultaneous quantification was carried out for a plurality of samples in the same manner as in Experimental Example 5, and the results are shown in FIG.

[0205] A protein (albumin) present in a human body sample was selected. An aptamer specific to the protein was prepared, and an aptamer-MNP complex was prepared in the same manner as in Preparation Example 4. Next, as in Experimental Example 5, the prepared aptamer-MNP complex was placed in separate wells 1 to 4, and human blood requiring diagnosis was then placed in each well for reaction. After the reaction was completed, each well was subjected to a magnetic field treatment as shown in Figure 23. As a result, impurities other than the protein that specifically bound to the aptamer could be removed from each well. Thereafter, CuCl 2 Reaction with each protein 1-4 and residual CuCl 2 The treatment of each well with the complex compound represented by formula 10 and the removal of the remaining complex compound are sequentially performed to obtain [M] as shown in FIG. n -L 1 -N 1-Only the complex of analyte-second binding part-carrier was left in the well, and M applied a different sequence for each sample. After that, trypsin was treated in each well and filtered to obtain peptides. As a result of analyzing the obtained peptides with a mass spectrometer, the polymer of the detection sensor treated in well 1 was composed of peptides with a residence time (RT) of 14 minutes, the polymer of the detection sensor treated in well 2 was composed of peptides with a residence time (RT) of 17.5 minutes, the polymer of the detection sensor treated in well 3 was composed of peptides with a residence time (RT) of 21.5 minutes, and the polymer of the detection sensor treated in well 4 was composed of peptides with a residence time (RT) of 24.5 minutes. It was found that the expression level exceeded the normal reference value for samples 1, 2, and 4, but the expression level was normal for sample 3, and therefore it was found that the detection sensor has excellent high-sensitivity simultaneous detection capability for analytes in biological samples even in simultaneous measurement of multiple samples.

[0206] [Experimental Example 6] Confirmation of diagnostic capabilities using detection sensors (3) In order to confirm the diagnostic capability of the detection sensor of the present invention, albumin was prepared as an analyte and then prepared at concentrations of 0, 0.33 ug / ul, 0.65 ug / ul, and 1.3 ug / ul. Thereafter, in order to detect albumin, a peptide specific to albumin (CB3GA)-rhodamine-(SLVPR (SEQ ID NO: 689)) having the structure shown in FIG. 24 was used. 5 The complex compound was prepared. After that, the complex compound was reacted with albumin in an equivalent ratio of 3 to 6, and the unreacted compound was removed. Then, as shown in FIG. 25, trypsin was treated (SLVPR). 5 The peptide compound was fragmented into SLVPR, and the change in sensitivity depending on the concentration of the analyte was measured using a mass spectrometer, and the results are shown in Figure 27. However, in order to compare the diagnostic ability of the detection sensor of the present invention, the fluorescence intensity of rhodamine was measured before trypsin treatment as shown in Figure 26, and the results are shown in Figure 28.

[0207] As shown in Figures 27 and 28, for the detection of albumin, a peptide polymer in which the SLVPR peptide fragment is repeated five times ((SLVPR) 5 When the ELISA kit was used, the peptide polymer was cleaved into five SLVPR peptide fragments by trypsin treatment, thereby exerting an amplification effect. In particular, it was confirmed that the sensitivity was increased by more than 6.5 times compared to the fluorescence measurement method.

[0208] Thus, through the examples of the present invention, it was confirmed that the detection sensor of the present invention can detect analytes with high sensitivity through amplification, and that simultaneous detection is also possible by producing peptides with diverse sequences.

Claims

1. A composition for detecting or measuring an analyte by mass spectrometry, comprising a conjugate compound represented by the following formula 1: [0010] In the above formula 1, n is an integer from 2 to 100,000; M is a repeatable unit compound selected from the group consisting of amino acids, amino acid analogs, peptides, peptide analogs, monosaccharides, oligosaccharides, and polysaccharides; L １ is a direct bond or a linker; N １ is a first binding moiety that binds to the analyte, The bond between M and M is cleaved by a catalyst to allow M to be detected or measured upon detection or measurement of the analyte.

2. 2. The composition of claim 1, wherein the mass-to-charge ratio (m / z) of M is from 30 to 3000.

3. The composition of claim 1, wherein M is represented by formula 2: [0025] In the above formula 2, m is an integer from 1 to 100,000; and X １ ~X ｍ are each independently a unit selected from the group consisting of an amino acid, an amino acid analog, a peptide, a peptide analog, a monosaccharide, an oligosaccharide, and a polysaccharide.

4. The X １ Or X ｍ The composition of claim 3 , wherein is isoleucine, lysine, serine, arginine or threonine.

5. The composition according to claim 1 , wherein the first binding portion comprises at least one selected from the group consisting of a probe, an antisense nucleotide, an antibody, an oligopeptide, a ligand, a peptide nucleic acid (PNA), and an aptamer that binds to the analyte.

6. The composition according to claim 1, wherein the first binding portion comprises one or more selected from the group consisting of Chemical Formulas 1 to 5: [Formula 1] [Case 2] [C3] [C4] [C5] In the above Chemical Formulas 1 to 5, p is an integer from 7 to 20; * indicates the above [M] ｎ Or the above L １ This is the site that is linked to

7. Said L １ The composition of claim 1, wherein when is a linker, the linker comprises one or more selected from formulae 6 to 8: [C6] [C7] [C8] In the above Chemical Formulas 6 to 8, q is an integer of 1 or more and 5 or less; * indicates the part where the linkage is made.

8. The composition according to claim 1 , comprising two or more different conjugate compounds represented by formula 1.

9. A kit for detecting an analyte, comprising the composition according to any one of claims 1 to 8, The kit is for use in mass spectrometry.

10. The kit for detecting an analyte according to claim 9 , further comprising a second binding moiety that binds to the analyte, an immobilizer, a carrier, biotin, a washing solution, or a reaction solution.

11. The kit for detecting an analyte according to claim 10 , wherein the kit comprises two or more different second binding moieties.

12. The kit for detecting an analyte according to claim 10, wherein the second binding portion comprises at least one selected from the group consisting of a probe, an antisense nucleotide, an antibody, an oligopeptide, a ligand, a peptide nucleic acid (PNA), and an aptamer, which specifically bind to the analyte.

13. The reaction solution contains CuCl ２ , Cu(NO ３ ) ２ , CoCl ２ , Co(NO ３ ) ２ , Zn(NO ３ ) ２ and ZnCl ２ The kit for detecting an analyte according to claim 10, which comprises one or more metal salts selected from the group consisting of:

14. A reaction step of reacting an analyte with a composition for detecting or measuring the analyte, the composition comprising a complex compound represented by formula 1; A method for analyzing an analyte, comprising: a detection step of detecting or measuring M in a complex compound contained in the composition; [0030] In the above formula 1, n is an integer from 2 to 100,000; M is a repeatable unit compound selected from the group consisting of amino acids, amino acid analogs, peptides, peptide analogs, monosaccharides, oligosaccharides, and polysaccharides; L １ is a direct bond or a linker; N １ is a first binding moiety that binds to the analyte.

15. 15. The method of claim 14, wherein the analyte is present in a biological sample isolated from an individual of interest.

16. The analytical method according to claim 15, further comprising an immobilization step of contacting the analyte with a second binding moiety and immobilizing the analyte.

17. The method according to claim 16, wherein the second binding portion comprises at least one selected from the group consisting of a probe, an antisense nucleotide, an antibody, an oligopeptide, a ligand, a peptide nucleic acid (PNA), and an aptamer, which specifically bind to the analyte.

18. The analytical method according to claim 17, wherein the second binding portion binds to an immobilizer, a carrier, or biotin to form a second binding portion-immobilizer complex or a second binding portion-carrier complex.

19. The analytical method according to claim 14, further comprising a cleavage step of cleaving M units in the complex compound after the reaction step.

20. The method according to claim 19, wherein the cleavage step is performed by an enzyme or a synthetic catalyst to cleave the M unit body.

21. During the cleavage step, [M] in the complex compound ｎ The method of claim 20, wherein M is cleaved into n M units to increase the sensitivity of detection or measurement of M.

22. 15. The analytical method of claim 14, further comprising the step of treating a metal salt during the reacting step.

Images