Sialoadhesin

Sialoadhesin prefers a(2 3)-linked sialosides, which are abundant on cell surfaces and specifically recognizes the Neu5Ac moiety. [37], The binding affinity of sialoadhesin to the simple methyl sialoside 3 (Fig. 18.4a) is in the millimolar range, and replacement of methyl group with benzyl (Bn) in the form of compound 4 improved 

FIGURE 18.4 Modified sialosides used in determining high-affinity ligands for sialoadhesin. (a) Sialosides modified at 2- and 5-positions, (b) Methyl sialosides modified at C9. (c) A high-affinity ligand for sialoadhesin. 

FIGURE 18.5 Some C9-modified sialosides and their comparative potencies. 

TABLE 18.2 Comparison of Inhibitory Potential of Synthetic Sialosides [36,40] 

Sialoside Human CD22 Mouse CD22 Mouse Sialoadhesin 

Possible functions for sialoadhesin have been implicated in the development of myeloid cells in the bone marrow and the trafficking of leukocytes in lymphatic organs (Crocker et al., 1991, 1992 van den Berg et al., 1992). Evidence 

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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... 

Kelm, S., Pelz, A., Schauer, R. etal. Sialoadhesin, myelin-associated glycoprotein and CD22 define a new family of sialic acid-dependent adhesion molecules of the immunoglobulin superfamily. Curr. Biol. 4 965-972,1994. 

Calciflations were performed using the crystallographic structure of the sialyl lactose-sialoadhesin complex, PDB crystal structure entry IQFO [64]. 

Fig. 7 Comparison of experimental and predicted STD values from CORCEMA-ST protocol for the crystal structure of sialoadhesin-sialyl lactose complex at protein/ligand ratio of 1 300. Reprinted from [63] 2004, with permission from Elsevier...

Acknowledgements This work was supported in part by the NCI grant CA-13148. The authors wish to thank Prof. B. Mario Pinto for supplying the originals of some figmes used in this review. The work on sialoadhesin/sialyllactose and UDP-Gal/galctosyltransferase complexes was from a fruitful collaboration with Prof. Thomas Peters at the Medical University of Liibeck. 

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... 

Halkes KM, St Hilaire PM, Crocker PR, Meldal M, Glycopeptides as oligosaccharide mimics high affinity sialopeptide ligands for sialoadhesin from combinatorial libraries, J. Comb. Chem., 5(1) 18-27, 2003. 

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