Abstract:
:Oligo/polysialic acids consisting of consecutive α(2,8)-linkages on gangliosides and glycoproteins play a role in cell adhesion and differentiation events in a manner that is dependent on the degree of polymerization (DP). Anti-oligo/polysialic acid antibodies often have DP-dependent antigenic specificity, and such unique antibodies are often used in biological studies for the detection and differentiation of oligo/polysialic acids. However, molecular mechanisms remain unclear. We here use NMR techniques to analyze the binding epitopes of the anti-oligo/polysialic acid monoclonal antibodies (mAb) A2B5 and 12E3. The mAb A2B5, which has a preference for trisialic acid, recognizes sialic acid residues at the non-reducing terminus and those in nascent units. On the other hand, mAb 12E3, which prefers oligo/polysialic acids of more than six sugar units, recognizes inner sialic acid residues. In both structural complexes, the interresidue transferred NOE correlations are significantly different from those arising from analogs of the free states, indicating that the bound and free sugar conformations are distinct. The ability of the two mAbs to distinguish the chain lengths comes from different binding epitopes and possibly from the conformational differences in the oligo/polysialic acids. Information on the recognition modes is needed for the structural design of immunoreactive antigens for the development of high-affinity anti-polysialic acid antibodies and of related vaccines against pathogenic, polysialic acid-coated bacteria.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Hanashima S,Sato C,Tanaka H,Takahashi T,Kitajima K,Yamaguchi Ydoi
10.1016/j.bmc.2013.07.023subject
Has Abstractpub_date
2013-10-01 00:00:00pages
6069-76issue
19eissn
0968-0896issn
1464-3391pii
S0968-0896(13)00634-2journal_volume
21pub_type
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