Sialoside Specificity of the Siglec Family Assessed Using Novel Multivalent Probes

Ten of the 11 known human siglecs or their murine orthologs have been evaluated for their specificity for over 25 synthetic sialosides representing most of the major sequences terminating carbohydrate groups of glycoproteins and glycolipids. Analysis has been performed using a novel multivalent platform comprising biotinylated sialosides bound to a streptavidin-alkaline phosphatase conjugate. Each siglec was found to have a unique specificity for binding 16 different sialoside-streptavidin-alkaline phosphatase probes. The relative affinities of monovalent sialosides were assessed for each siglec in competitive inhibition studies. The quantitative data obtained allows a detailed analysis of each siglec for the relative importance of sialic acid and the penultimate oligosaccharide sequence on binding affinity and specificity. Most remarkable was the finding that myelin-associated glycoprotein (Siglec-4) binds with 500–10,000-fold higher affinity to a series of mono- and di-sialylated derivatives of the O-linked T-antigen (Galβ(1–3)-GalNAcαOThr) as compared with α-methyl-NeuAc.

[1]  J. Paulson,et al.  Biocatalytic Preparation of N‐Glycolylneuraminic Acid, Deaminoneuraminic Acid (KDN) and 9‐Azido‐9‐deoxysialic Acid Oligosaccharides , 2003 .

[2]  A. Varki,et al.  Cloning, Characterization, and Phylogenetic Analysis of Siglec-9, a New Member of the CD33-related Group of Siglecs , 2000, The Journal of Biological Chemistry.

[3]  M. Augustus,et al.  Characterization of siglec-5, a novel glycoprotein expressed on myeloid cells related to CD33. , 1998, Blood.

[4]  A. May,et al.  Crystal structure of the N-terminal domain of sialoadhesin in complex with 3' sialyllactose at 1.85 A resolution. , 1998, Molecular cell.

[5]  A. Varki,et al.  Cloning and Characterization of Human Siglec-11 , 2002, The Journal of Biological Chemistry.

[6]  M. Neuberger,et al.  Interaction of CD22 with α2,6‐linked sialoglycoconjugates: innate recognition of self to dampen B cell autoreactivity? , 2002, European journal of immunology.

[7]  A. Suzuki,et al.  A streptavidin-based neoglycoprotein carrying more than 140 GT1b oligosaccharides: quantitative estimation of the binding specificity of murine sialoadhesin expressed on CHO cells. , 1998, Journal of biochemistry.

[8]  Matthew L. Thomas,et al.  The sialoadhesin CD33 is a myeloid‐specific inhibitory receptor , 1999, European journal of immunology.

[9]  T. Yamaji,et al.  A Small Region of the Natural Killer Cell Receptor, Siglec-7, Is Responsible for Its Preferred Binding to α2,8-Disialyl and Branched α2,6-Sialyl Residues , 2002, The Journal of Biological Chemistry.

[10]  M. Hancock,et al.  I-type lectins. , 2002 .

[11]  I. Wilson,et al.  Single amino acid substitutions in influenza haemagglutinin change receptor binding specificity , 1983, Nature.

[12]  T. Norberg,et al.  Thioglycosides as glycosylating agents in oligosaccharide synthesis , 1987, Glycoconjugate Journal.

[13]  J. Manuguerra,et al.  Modifications of cell surface sialic acids modulate cell adhesion mediated by sialoadhesin and CD22 , 1994, Glycoconjugate Journal.

[14]  P. Crocker,et al.  Characterization of CD33 as a new member of the sialoadhesin family of cellular interaction molecules. , 1995, Blood.

[15]  G M Whitesides,et al.  Hemagglutinins from two influenza virus variants bind to sialic acid derivatives with millimolar dissociation constants: a 500-MHz proton nuclear magnetic resonance study. , 1989, Biochemistry.

[16]  Jason K. Pontrello,et al.  Synthesis of a multivalent display of a CD22-binding trisaccharide. , 2002, Carbohydrate research.

[17]  S. Gordon,et al.  Sialoadhesin, a macrophage sialic acid binding receptor for haemopoietic cells with 17 immunoglobulin‐like domains. , 1994, The EMBO journal.

[18]  A. Fournier,et al.  Myelin-Associated Glycoprotein as a Functional Ligand for the Nogo-66 Receptor , 2002, Science.

[19]  R. Brossmer,et al.  The Ligand-binding Domain of CD22 Is Needed for Inhibition of the B Cell Receptor Signal, as Demonstrated by a Novel Human CD22-specific Inhibitor Compound , 2002, The Journal of experimental medicine.

[20]  D. Fearon,et al.  A role in B cell activation for CD22 and the protein tyrosine phosphatase SHP. , 1995, Science.

[21]  Zhenbao Yu,et al.  Identification and Characterization of S2V, a Novel Putative Siglec That Contains Two V Set Ig-like Domains and Recruits Protein-tyrosine Phosphatases SHPs* , 2001, The Journal of Biological Chemistry.

[22]  W. Wakarchuk,et al.  Efficient preparation of natural and synthetic galactosides with a recombinant beta-1,4-galactosyltransferase-/UDP-4'-gal epimerase fusion protein. , 2001, The Journal of organic chemistry.

[23]  D. Sgroi,et al.  CD22, a B cell-specific immunoglobulin superfamily member, is a sialic acid-binding lectin. , 1993, The Journal of biological chemistry.

[24]  L. Mckerracher.  Ganglioside rafts as MAG receptors that mediate blockade of axon growth , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[25]  P. Moore,et al.  Identification, characterization and leucocyte expression of Siglec-10, a novel human sialic acid-binding receptor. , 2001 .

[26]  T. Norberg,et al.  Synthesis of mono- and disaccharide amino-acid derivatives for use in solid phase peptide synthesis , 2005, Glycoconjugate Journal.

[27]  Yoshihiro Kawaoka,et al.  Sialic Acid Species as a Determinant of the Host Range of Influenza A Viruses , 2000, Journal of Virology.

[28]  A. Varki,et al.  Siglecs, sialic acids and innate immunity. , 2001, Trends in immunology.

[29]  J. Skehel,et al.  Proton nuclear magnetic resonance studies of the binding of sialosides to intact influenza virus. , 1992, Virology.

[30]  A. Varki,et al.  New Aspects of Siglec Binding Specificities, Including the Significance of Fucosylation and of the Sialyl-Tn Epitope* , 2000, The Journal of Biological Chemistry.

[31]  K. Cheng,et al.  A new siglec family member, siglec-10, is expressed in cells of the immune system and has signaling properties similar to CD33. , 2001, European journal of biochemistry.

[32]  T. Yamashita,et al.  The p75 receptor transduces the signal from myelin-associated glycoprotein to Rho , 2002, The Journal of cell biology.

[33]  Y. Lee,et al.  Glycamine formation via reductive amination of oligosaccharides with benzylamine: efficient coupling of oligosaccharides to protein. , 1994, Carbohydrate research.

[34]  High Resolution Crystal Structures of Siglec-7 , 2003, The Journal of Biological Chemistry.

[35]  Zhenbao Yu,et al.  mSiglec-E, a novel mouse CD33-related siglec (sialic acid-binding immunoglobulin-like lectin) that recruits Src homology 2 (SH2)-domain-containing protein tyrosine phosphatases SHP-1 and SHP-2. , 2001 .

[36]  M. Kiso,et al.  MyeliN‐associated Glycoprotein Binding to Gangliosides: Structural Specificity and Functional Implications a , 1998, Annals of the New York Academy of Sciences.

[37]  A. Varki,et al.  CD22-mediated Cell Adhesion to Cytokine-activated Human Endothelial Cells , 1995, The Journal of Biological Chemistry.

[38]  J. Skehel,et al.  Host-mediated selection of influenza virus receptor variants. Sialic acid-alpha 2,6Gal-specific clones of A/duck/Ukraine/1/63 revert to sialic acid-alpha 2,3Gal-specific wild type in ovo. , 1985, The Journal of biological chemistry.

[39]  N. Bovin,et al.  Glycan specificity of myelin-associated glycoprotein and sialoadhesin deduced from interactions with synthetic oligosaccharides. , 1998, European journal of biochemistry.

[40]  C. Buckley,et al.  The Myeloid-specific Sialic Acid-binding Receptor, CD33, Associates with the Protein-tyrosine Phosphatases, SHP-1 and SHP-2* , 1999, The Journal of Biological Chemistry.

[41]  S. Sabesan,et al.  Characterization of Sialyloligosaccharide Binding by Recombinant Soluble and Native Cell-associated CD22 , 1995, The Journal of Biological Chemistry.

[42]  J. Marth,et al.  Constitutively unmasked CD22 on B cells of ST6Gal I knockout mice: novel sialoside probe for murine CD22. , 2002, Glycobiology.

[43]  E. Davies,et al.  Comparison of CD22 binding to native CD45 and synthetic oligosaccharide , 2002, European journal of immunology.

[44]  R. Autar,et al.  A Structure-Function Study of Ligand Recognition by CD22β* , 2001, The Journal of Biological Chemistry.

[45]  P. Klenerman,et al.  Identification and Characterization of a Novel Siglec, Siglec-7, Expressed by Human Natural Killer Cells and Monocytes* , 1999, The Journal of Biological Chemistry.

[46]  D. McVicar,et al.  Myeloid specific human CD33 is an inhibitory receptor with differential ITIM function in recruiting the phosphatases SHP-1 and SHP-2. , 2000, Blood.

[47]  A. Varki,et al.  Natural ligands of the B cell adhesion molecule CD22 beta can be masked by 9-O-acetylation of sialic acids , 1994, The Journal of cell biology.

[48]  M. Thomas,et al.  Molecular Cloning of MIS, a Myeloid Inhibitory Siglec, That Binds Protein-tyrosine Phosphatases SHP-1 and SHP-2* , 2001, The Journal of Biological Chemistry.

[49]  M. Kiso,et al.  Binding Specificities of the Sialoadhesin Family of I-type Lectins , 1997, The Journal of Biological Chemistry.

[50]  O. Blixt,et al.  Solid-Phase Enzymatic Synthesis of a Lewis a Trisaccharide Using an Acceptor Reversibly Bound to Sepharose , 1997 .

[51]  L. Facci,et al.  Myelin-associated Glycoprotein Interacts with Ganglioside GT1b , 2001, Journal of Biological Chemistry.

[52]  M. Schachner,et al.  Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[53]  B. Neel,et al.  Sialic Acid Binding Domains of CD22 Are Required For Negative Regulation of B Cell Receptor Signaling , 2002, The Journal of experimental medicine.

[54]  M. Schachner,et al.  Crucial Role for the Myelin‐associated Glycoprotein in the Maintenance of Axon‐Myelin Integrity , 1995, The European journal of neuroscience.

[55]  P. Crocker,et al.  Siglec-9, a Novel Sialic Acid Binding Member of the Immunoglobulin Superfamily Expressed Broadly on Human Blood Leukocytes* , 2000, The Journal of Biological Chemistry.

[56]  R. Biassoni,et al.  Identification and Molecular Cloning of P75/Airm1, a Novel Member of the Sialoadhesin Family That Functions as an Inhibitory Receptor in Human Natural Killer Cells , 1999, The Journal of experimental medicine.

[57]  P. Crocker,et al.  Siglecs: sialic-acid-binding immunoglobulin-like lectins in cell-cell interactions and signalling. , 2002, Current opinion in structural biology.

[58]  R. Webster,et al.  Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates. , 1994, Virology.

[59]  T. Norberg,et al.  Solid phase synthesis of the fibronectin glycopeptide V(Galβ3GalNAcα)THPGY, its β analogue, and the corresponding unglycosylated peptide , 1991, Glycoconjugate Journal.

[60]  P. Crocker,et al.  New Functions for the Sialic Acid‐Binding Adhesion Molecule CD22, a Member of the Growing Family of Siglecs , 2001, Scandinavian journal of immunology.

[61]  R. Brossmer,et al.  Functional groups of sialic acids involved in binding to siglecs (sialoadhesins) deduced from interactions with synthetic analogues. , 1998, European journal of biochemistry.

[62]  A. Varki,et al.  Siglec-7: a sialic acid-binding lectin of the immunoglobulin superfamily. , 2000, Glycobiology.

[63]  J. Paulson,et al.  Efficient chemoenzymatic synthesis of O-linked sialyl oligosaccharides. , 2002, Journal of the American Chemical Society.

[64]  M. Filbin,et al.  Sialic Acid Specificity of Myelin-associated Glycoprotein Binding* , 1997, The Journal of Biological Chemistry.

[65]  S. Watt,et al.  Human Siglec‐5: tissue distribution, novel isoforms and domain specificities for sialic acid‐dependent ligand interactions , 2002, British journal of haematology.

[66]  A. Varki,et al.  Masking and unmasking of the sialic acid-binding lectin activity of CD22 (Siglec-2) on B lymphocytes. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[67]  Nan Li,et al.  Cloning and Characterization of Siglec-10, a Novel Sialic Acid Binding Member of the Ig Superfamily, from Human Dendritic Cells* , 2001, The Journal of Biological Chemistry.

[68]  E. B. D. Brinkman-van der Linden,et al.  Loss of N-Glycolylneuraminic Acid in Human Evolution , 2000, The Journal of Biological Chemistry.

[69]  Marco Domeniconi,et al.  Myelin-Associated Glycoprotein Interacts with the Nogo66 Receptor to Inhibit Neurite Outgrowth , 2002, Neuron.

[70]  M. Filbin,et al.  Sialoadhesin, myelin-associated glycoprotein and CD22 define a new family of sialic acid-dependent adhesion molecules of the immunoglobulin superfamily , 1994, Current Biology.

[71]  R. Chammas,et al.  Sialic Acid 9-O-Acetylation on Murine Erythroleukemia Cells Affects Complement Activation, Binding to I-type Lectins, and Tissue Homing* , 1996, The Journal of Biological Chemistry.

[72]  R. Brossmer,et al.  Fibronectin is a binding partner for the myelin‐associated glycoprotein (siglec‐4a) , 2001, FEBS Letters.

[73]  Jian Ni,et al.  Siglec-8 , 2000, The Journal of Biological Chemistry.

[74]  M. Kiso,et al.  Gangliosides are neuronal ligands for myelin-associated glycoprotein. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[75]  M. López-Botet,et al.  Cloning of two new splice variants of Siglec-10 and mapping of the interaction between Siglec-10 and SHP-1. , 2002, Biochemical and biophysical research communications.

[76]  L. Mckerracher,et al.  Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth , 1994, Neuron.