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Two Related but Distinct Chondroitin Sulfate Mimetope Octasaccharide Sequences Recognized by Monoclonal Antibody WF6

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Title: Two Related but Distinct Chondroitin Sulfate Mimetope Octasaccharide Sequences Recognized by Monoclonal Antibody WF6
Authors: Pothacharoen, Peraphan Browse this author
Kalayanamitra, Kittiwan Browse this author
Deepa, Sarama Browse this author
Fukui, Shigeyuki Browse this author
Hattori, Tomohide Browse this author
Fukushima, Nobuhiro Browse this author
Hardingham, Timothy Browse this author
Kongtawelert, Prachya Browse this author
Sugahara, Kazuyuki Browse this author →KAKEN DB
Keywords: chondroitin sulfate
epitope
monoclonal antibody
octasaccharides
sulfation
molecular modeling
Issue Date: 30-Nov-2007
Journal Title: Journal of Biological Chemistry
Volume: 282
Issue: 48
Start Page: 35232
End Page: 35246
Publisher DOI: 10.1074/jbc.M702255200
PMID: 17884822
Abstract: Chondroitin sulfate (CS) proteoglycans are major components of cartilage and other connective tissues. The monoclonal antibody (mAb) WF6, developed against embryonic shark cartilage CS, recognizes an epitope in CS chains, which is expressed in ovarian cancer and variably in joint diseases. To elucidate the structure of the epitope, we isolated oligosaccharide fractions from a partial chondroitinase ABC digest of shark cartilage CS-C and established their chain length, disaccharide composition, sulfate content and sulfation pattern. These structurally defined oligosaccharide fractions were characterized for binding to WF6 by enzyme-linked immunosorbent assay using an oligosaccharide microarray prepared with CS oligosaccharides derivatized with a fluorescent aminolipid. The lowest molecular weight fraction recognized by WF6 contained octasaccharides, which were split into five subfractions. The most reactive subfraction contained several distinct octasaccharide sequences. Two octasaccharides, **」GD-C-C-C and 」GC-C-A-D, were recognized by WF6, but other related octasaccharides, 」GC-A-D-C and 」GC-C-C-C, were not. The structure and sequences of both the binding and non-binding octasaccharides were compared by computer modeling, which revealed a remarkable similarity between the shape and distribution of the electrostatic potential in the two different octasaccharide sequences that bound to WF6 and which differed from the non-binding octasaccharides. The strong similarity in structure predicted for the two binding CS octasaccharides (」GD-C-C-C and 」GC-C-A-D) provided a possible explanation for their similar affinity for the WF6, although they differed in sequence and thus form two specific mimetopes for the antibody. **Abbreviations: A, GlcUAυ1-3GalNAc(4-O-sulfate); C, GlcUAυ1-3GalNAc(6-O-sulfate); D, GlcUA(2-O-sulfate)υ1-3GalNAc(6-O-sulfate); 」GC, 」G4,5HexUAτ1-3GalNAc(6-O-sulfate); 」GD, 」G4,5HexUA(2-O-sulfate)τ1-3GalNAc(6-O-sulfate).
Type: article (author version)
URI: http://hdl.handle.net/2115/44203
Appears in Collections:生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 菅原 一幸

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