Siglecs sialoadhesin

Kelm, S, Brossmer, R, Isecke, R, Gross, H J, Strenge, K, Schauer, R, Functional groups of siahc acids involved in binding to siglecs (sialoadhesins) deduced from interactions with synthetic analogues, Eur. J. Biochem., 255, 663-672, 1998. 

The siglecs constitute a novel subfamily of immunoglobulin-like molecules that bind to sialosides. These molecules, previously termed sialoadhesins, share considerable sequence similarity among the first four amino-terminal Ig domains [8,9]. More importantly, all members... 

Studies of sialoadhesin and sialoside interactions by NMR provided evidence that the molecular interactions characterized in crystals also occur in solution [39], Although the binding between natural sialosides and siglecs is relatively weak, increased binding affinity has been seen for sialoadhesin, MAG, and CD22 using... 

Siglec-1 Sn (Sialoadhesin) Macrophages in spleen, lymph nodes, and bone marrow Neu5Ac-a(2-3)-Gal-P(l-3/4)-GlcAAc- Neu5Ac-a(2-3)-Gal-P(l-3)-GaL/VAc-... 

In order to elucidate the extended glycoconjugate binding specifities of MAG and other siglecs (Schwann cell myelin protein [SMP] and sialoadhesin [Sn]), Schnaar et al. [26a,27b] measured the siglec-mediated half-maximal cell adhesion to several immobilized natural and synthetically modified gangliosides (Table 16.2) [29]. 

The interesting chemistry of sialic acid has been discussed in several reviews [213,214,215]. Sialic acid is an important component of complex oligosaccharides, when it is placed in the terminal position, and often masks the penultimate saccharide sequences. In this position, it interacts with numerous receptors including the influenza virus neuraminidase, and receptors mediating intercellular interactions such as the selectins (members of the C-t) e animal lectin family) and siglecs (or sialoadhesins, members of the immunoglobulin superfamily). The structure of influenza B neuraminidase in complex with sialic acid has been solved by X-ray crystallography at 2.2 A resolution (O Fig. 17) [216]. 

Zaccai, N. R. Maenaka, K. Maenaka, T. Crocker, P. R. Brossmer, R. Kelm, S. Jones, E. Y., Structure-guided design of sialic acid-based Siglec inhibitors and crystallographic analysis in complex with sialoadhesin. Structure (Comb) 2003,11, (5), 557-67. 

In M effort to compare the glycan specificity of MAG (Siglec-4) and sialoadhesin (Sn, Siglec-1), Kelm et al. studied their interactions with a series of synthetic monovalent oligosaccharides using a hapten inhibition assay (Table 2) [27]. Native human erythrocytes were incubated with antibody-complexed MAG ii.s-Fc in the... 

MAG [66] based on the X-ray structure of sialoadhesin (Siglec-1) [26] indicated that the carboxylic acid of the a(2-6)-linked siaUc acid forms a second salt bridge with Lys67 (Fig. 5). Finally, the comparably low STD values found for the protmis of the GaWAc residue (Fig. 4) indicated that no significant contribution to binding originates fi om this moiety of tetrasaccharide 67. 

Fig. 5 Homology model of MAG - based on a 3D-stracture of sialoadhesin (Siglec-1) [26] complexed with tetrasaccharide 67 (left) and glycomimetic 85 (right) [66, 70]...

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