National Institute of Advanced Industrial Science and Technology

Seikagaku Kogyo Kabushiki Kaisha

National Center for Global Health and Medicine

Tokyo Medical University

Sysmex Corporation

Nagoya University

Seikagaku Corporation

University of Tsukuba

Glytech, Inc.

The University of Toyama

Public University Corporation Nagoya City University

Science & Technology Corporation

Glycobiomarker Leading Innovation Co., Ltd.

National Institute of Advanced Industrial

Nagoya City University

Hisashi Narimatsu

Akira Togayachi

Yuzuru Ikehara

Takashi Sato

Atsushi Kuno

Hiroyuki Kaji

Yasunori Chiba

Maki Sogabe

Masanori Goto

Niro Inaba

Koji Kimata

Jun Hirabayashi

Masashi Mizokami

Toshikazu Yada

Toru Hiruma

Takashi Ohkura

Hideki Matsuzaki

Masayuki Noguchi

Hideo Mochizuki

Masaharu Nomura

Hiroaki Tateno

Yasuhito Tanaka

Shigemi Sugioka

Tomomi Kubota

Hiromichi Sawaki

Hayao Nakanishi

Toru Nakanishi

Yoshitoshi Hirao

Yasuhiro Hashimoto

Keiro Shirotani

Yasuko Ishizuka

Jun Iwaki

Masanori Gotoh

Minako Abe

Hiromi Ito

Kazuhiro Fukae

Satoshi Murakami

Shinya Nagai

Youichi Takahama

Chikayuki Tsuruno

Yoshie Takahashi

Tatsuhiko Ozawa

Toshihide Shikanai

Kyoka Hoshi

Makoto Ochou

Kiyoaki Ito

Shunsuke Matsubara

Takashi Kagawa

Satoshi Futakawa

Atsushi Matsuda

Junichi Shoda

Hajime Arai

Toru Kawamoto

Masakazu Miyajima

Kiyomitsu Nara

Kazuo Fujihara

Takashi Kudo

Toshie Iwai

Yoshinobu Kariya

Takashi Angata

Kiyohiko Angata

Hiroki Shimizu

Takanori Wagatsuma

Masaaki Korenaga

Kazuto Tajiri

An examination system that recognizes a glycosylated antigen in Dane particles of hepatitis B virus (HBV) and a neutralizing antibody that recognizes the glycosylated antigen and that exhibits an infection-inhibiting activity. It was elucidated that Dane particles are associated with specific glycan structures, and this enabled the construction of a new detection system for infectious, i.e., nucleic acid-containing, hepatitis B virus particles and the provision of a neutralizing antibody that recognizes a glycosylated antigen and that exhibits an infection-inhibiting activity.

Method for efficiently inducing antibody, antibody and detection system for hepatitis virus

An object of the present invention is to develop and provide a lung cancer differential marker with which lung cancer can be diagnosed conveniently and highly sensitively without depending only on increase or decrease in protein expression level between cancer patients and healthy persons. Another object of the present invention is to develop and provide a glycan marker capable of distinguishing histological types of lung cancer. Of serum glycoproteins, glycopeptide and glycoprotein groups whose glycan structures were altered specifically in lung cancer cell culture supernatants were identified, and they are provided as lung cancer differential markers.

Lung cancer differential marker

Amonomeric lectin polypeptide is provided. Themonomeric lectin polypeptide includes any one of the amino acid sequences selected from the group consisting of: (1) the amino acid sequence represented by SEQ ID NO: 2; (2) the amino acid sequence defined in (1) above, except that one to 20 amino acids at positions other than Cys272 position is/are deleted, substituted, inserted, or added; and (3) the amino acid sequence defined in (1) or (2) above, further having an N-terminus deletion of one to 30 amino acids, in which Cys272 is alkylated, and the polypeptide is capable of specifically binding to a GalNAc terminal sugar chain.

Modified lectin derived from Wisteria floribunda

It is intended to develop and provide a method for detecting a particular glycan-isoform rapidly and specifically by a small number of steps. The present invention provides a glycan-isoform detection method comprising quantifying an immune complex formed by the mixing of a test sample with a sugar chain non-reducing terminal residue-binding lectin and an antibody specifically binding to the protein moiety of the glycan-isoform, etc., comparing the obtained amount of the immune complex with the amount of a control immune complex obtained when a control sample is not mixed with the sugar chain non-reducing terminal residue-binding lectin or is mixed with a control protein, and determining the presence or absence of the glycan-isoform of interest in the test sample on the basis of the difference between these amounts.

Glycoform detection method and glycoform detection device

It is intended to find a highly specific epithelial ovarian cancer marker and to provide an antibody capable of specifically recognizing and detecting the marker or a fragment of the antibody. The present invention provides an anti-&#x3b2;1,6-N-acetylglucosaminyltransferase 5B antibody for diagnosis of epithelial ovarian cancer, i.e., an antibody for detection of a glycosyltransferase &#x3b2;1,6-N-acetylglucosaminyltransferase 5B as an epithelial ovarian cancer marker. The antibody recognizes, as an epitope, a part of a polypeptide of the enzyme consisting of the amino acid sequence represented by SEQ ID NO: 1.

Antibody for detecting epithelial ovarian cancer marker and method for diagnosing epithelial ovarian cancer

The purpose of the present invention is to develop: a method for selectively separating a glycoprotein derived from the central nervous system from a body fluid or a central nervous system cell; and a method for searching for an index marker for central nervous system diseases, which utilizes the aforementioned method. A protein derived from the central nervous system, which occurs in a trace amount in a body fluid or a central nervous system cell, can be selectively enriched by a two-stage separation procedure comprising removing a glycoprotein having sialic acid at a non-reducing terminal thereof from the body fluid or the central nervous system cell and then separating a glycoprotein having N-acetylglucosamine at a non-reducing terminal thereof.

Method for enrichment and separation of spinal fluid glycoprotein, method for searching for marker for central nervous system diseases which utilizes the aforementioned method, and marker for central nervous system diseases

The present invention provides an antibody capable of specifically recognizing and detecting the highly specific cancer marker with respect to the epithelial ovarian cancer, or a fragment of the antibody. The present invention provides an anti-&#x3b2;1,3-N-acetylglucosaminyltransferase 3 antibody for diagnosis of epithelial ovarian cancer, i.e., an antibody for detection of a glycosyltransferase &#x3b2;1,3-N-acetylglucosaminyltransferase 3 as an epithelial ovarian cancer marker. The antibody recognizes, as an epitope, a part of a polypeptide of the enzyme consisting of the amino acid sequence represented by SEQ ID NO: 1.

The present invention is directed to developing a glycan markers capable of detecting a hepatic disease, and more specifically to developing a glycan marker indicating a hepatic disease-state. Furthermore, the present invention is also directed to developing a glycan marker capable of distinguishing hepatic disease-states with the progress of hepatocarcinoma. The present inventors identified, among the serum glycoproteins, glycopeptides and glycoproteins in which a glycan structure specifically changes due to a hepatic diseases including hepatocarcinoma and provide these as novel glycan markers (glycopeptide and glycoprotein) specific to hepatic disease-states.

Glycan markers as measure of disease state of hepatic diseases

[Problem] The purpose of the present invention is to stably supply high-quality and highly uniformagglutinin (WFA) that recognizes biologically important sugar-chain markers, to elucidate the sugar-chain recognition activity in detail, and to furthermore increase the specificity of the sugar-chain recognition activity. [Solution] The present invention involves the development of a technique for cloning genes for codingagglutinin (WFA) and producing recombinant WFA having the same sugar-chain recognition activity as natural WFA from transformed bacteria. Natural WFA is reduced to thereby manufacture a reduced WFA monomer for specifically recognizing terminal GalNAc residue. A recombinant monomer WFA for recognizing LDN (GalNAc&#x3b2;1, 4GlcNAc) sugar chain, which is important as a diagnostic marker among sugar chains having a terminal GalNAc residue, is manufactured by introducing cysteine mutation to recombinant WFA or by C-terminal-side amino acid deletion.

[Problem to be Solved] The importance of sugar chains having &#x3b1;2,3- or &#x3b1;2,6-linked sialic acid at their non-reducing ends is known. Industrial production has been demanded for these sugar chain compounds. Particularly, the production of glycoprotein drugs or the like inevitably requires producing in quantity sugar chains having homogeneous structures by controlling the linking pattern (&#x3b1;2,6-linkage or &#x3b1;2,3-linkage) of sialic acid. Particularly, a triantennary or tetraantennary N-type complex sugar chain having sialic acid at each of all non-reducing ends is generally considered difficult to chemically synthesize. There has been no report disclosing that such a sugar chain was chemically synthesized. Furthermore, these sugar chains are also difficult to efficiently prepare enzymatically. [Solution] The present inventors have newly found the activity of sialyltransferase of degrading sialic acid on a reaction product in the presence of CMP and also found that formed CMP can be degraded enzymatically to thereby efficiently produce a sialic acid-containing sugar chain. The present inventors have further found that even a tetraantennary N-type sugar chain having four &#x3b1;2,6-linked sialic acid molecules, which has previously been difficult to synthesize, can be prepared at high yields by one-pot synthesis comprising the elongation reaction of a biantennary sugar chain used as a starting material without performing purification after each enzymatic reaction.

Method for producing sialic-acid-containing sugar chain

The present invention provides a novel endo-&#x3b2;-N-acetylglucosaminidase (Endo-Om) using a transformant produced by cloning an endo-&#x3b2;-N-acetylglucosaminidase (Endo-Om) gene originated from a methylotrophic yeastIFO10746 strain. The Endo-Om according to the present invention has a specific activity 13-fold higher than that of known Endo-M and a Vmax value 55-fold higher than that of the known Endo-M, and is useful for the analysis of the structures of sugar chains, including complex type sugar chains, in glycoproteins and the modification of the sugar chains. Also provided are an endo-&#x3b2;-N-acetylglucosaminidase (Endo-Cp), an endo-&#x3b2;-N-acetylglucosaminidase (Endo-Pa) and an endo-&#x3b2;-N-acetylglucosamimidase (Endo Zr) which are produced fromDL-1 ATCC26012 strain,ATCC36904 strain andATCC2623 strain, respectively, on the basis of an Endo-Om gene sequence, and each of which has a similar level of complex type sugar chain cleavage activity and a similar level of complex type sugar chain transfer activity to those of Endo-Om.

Complex type sugar chain hydrolase

An object of the present invention is to provide a method for measuring a glycan-marker glycoprotein, by which liver disease can be detected with higher accuracy than is possible with conventional methods. Also, an object of the present invention is to provide a method for examining liver disease, by which liver disease can be detected with higher accuracy than is possible with conventional methods. Disclosed is a method for measuring at least one glycoprotein selected from alpha-1-acid glycoprotein (AGP) and Mac-2-binding protein (M2BP) contained in a sample collected from a subject, comprising: measuring AGP binding to a first lectin selected from AOL and MAL, when the glycoprotein is AGP; and measuring M2BP binding to a second lectin selected from WFA, BPL, AAL, RCA120, and TJAII, when the glycoprotein is M2BP.

Method for measuring glycoprotein, method for examining liver disease, reagent for quantitative determination of glycoprotein, and glycan-marker glycoprotein as an index for clinical conditions of liver disease

A glycosaminoglycan sulfotransferase, a peptide thereof, a nucleic acid comprising a nucleotide sequence encoding the same, an enzyme agent for the synthesis of a glycosaminoglycan, which comprises the above-described enzyme or polypeptide, and a process for producing a glycosaminoglycan, which uses the enzyme agent.

Sulfotransferase, peptide thereof and DNA encoding the same

Disclosed are a method for early, sensitively and reliably detecting and distinguishing intrahepatic cholangiocarcinoma in a malignant tumor occurring primarily in the liver in a simple way, and a kit thereof. In the method, a glycan biomarker consisting of a lectin WFA (Wisteria floribunda Agglutinin)-binding glycoprotein derived from intrahepatic cholangiocarcinoma is used as a cancer marker to detect intrahepatic cholangiocarcinoma by detecting the cancer marker in a test specimen. The method for detecting intrahepatic cholangiocarcinoma can clearly differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma and enables early detection and determination with a performance clinically acceptable in terms of applicability, sensitivity and precision.

Method for detecting and distinguishing intrahepatic cholangiocarcinoma

Growing community of inventors

Tsukuba, Japan

Hisashi Narimatsu