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A novel monoclonal ...
A novel monoclonal antibody targeting carboxymethyllysine, an advanced glycation end product in atherosclerosis and pancreatic cancer
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- Wendel, Ulrika (author)
- University of Copenhagen
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- Persson, Nina (author)
- University of Copenhagen
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- Risinger, Christian (author)
- University of Copenhagen
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- Bengtsson, Eva (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine,Skåne University Hospital
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- Nodin, Björn (author)
- Lund University,Lunds universitet,Personlig patologi och cancerbehandling,Forskargrupper vid Lunds universitet,Personalized Pathology & Cancer Therapy,Lund University Research Groups
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- Danielsson, Lena (author)
- Lund University,Lunds universitet,Proteasinhibitorforskning,Forskargrupper vid Lunds universitet,Protease Inhibitor Research,Lund University Research Groups
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- Welinder, Charlotte (author)
- Lund University,Lunds universitet,CEBMMS PI,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Fredrikson, Gunilla Nordin (author)
- Lund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Skåne University Hospital
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- Jansson, Bo (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Blixt, Ola (author)
- University of Copenhagen
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(creator_code:org_t)
- 2018-02-08
- 2018
- English.
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:2
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Abstract
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- Advanced glycation end products are formed by non-enzymatic reactions between proteins and carbohydrates, causing irreversible lysine and arginine alterations that severely affect protein structure and function. The resulting modifications induce inflammation by binding to scavenger receptors. An increase in advanced glycation end products is observed in a number of diseases e.g. atherosclerosis and cancer. Since advanced glycation end products also are present in healthy individuals, their detection and quantification are of great importance for usage as potential biomarkers. Current methods for advanced glycation end product detection are though limited and solely measure total glycation. This study describes a new epitope-mapped single chain variable fragment, D1-B2, against carboxymethyllysine, produced from a phage library that was constructed from mouse immunizations. The phage library was selected against advanced glycation end product targets using a phage display platform. Characterization of its binding pattern was performed using large synthetic glycated peptide and protein libraries displayed on microarray slides. D1-B2 showed a preference for an aspartic acid, three positions N-terminally from a carboxymethyllysine residue and also bound to a broad collection of glycated proteins. Positive immunohistochemical staining of mouse atherosclerotic plaques and of a tissue microarray of human pancreatic tumors confirmed the usability of the new scFv for advanced glycation end product detection in tissues. This study demonstrates a promising methodology for high-throughput generation of epitope-mapped monoclonal antibodies against AGE.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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- By the author/editor
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Wendel, Ulrika
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Persson, Nina
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Risinger, Christ ...
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Bengtsson, Eva
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Nodin, Björn
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Danielsson, Lena
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Welinder, Charlo ...
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Fredrikson, Guni ...
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Jansson, Bo
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Blixt, Ola
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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PLoS ONE
- By the university
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Lund University