| Title |
-
en
Two Related but Distinct Chondroitin Sulfate Mimetope Octasaccharide Sequences Recognized by Monoclonal Antibody WF6
|
| Creator |
-
-
en
Pothacharoen, Peraphan
-
-
en
Kalayanamitra, Kittiwan
-
-
-
-
-
-
-
|
| Accessrights |
open access |
| Subject |
-
Other
en
chondroitin sulfate
-
Other
en
epitope
-
Other
en
monoclonal antibody
-
Other
en
octasaccharides
-
Other
en
sulfation
-
Other
en
molecular modeling
-
NDC
460
|
| Description |
-
Abstract
en
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).
|
| Date |
|
| Language |
|
| Resource Type |
journal article |
| Version Type |
AM |
| Identifier |
HDL
http://hdl.handle.net/2115/44203
|
| Relation |
-
isVersionOf
DOI
https://doi.org/10.1074/jbc.M702255200
-
PMID
17884822
|
| Journal |
-
en
Journal of Biological Chemistry
-
Volume Number282
Issue Number48
Page Start35232
Page End35246
|
| File |
|
| Oaidate |
2023-07-26 |
