Synthesis of a multivalent display of a CD22-binding trisaccharide.
Multivalent interactions have been implicated in the binding of B-cell surface glycoprotein CD22 to its physiological ligands. Because CD22 can influence B-cell antigen receptor (BCR) signaling, multivalent ligands that cluster CD22 may influence B-cell responses. Here, we report an efficient synthesis of a fluorophore-labeled multivalent display of a CD22-binding trisaccharide, Neu5Acalpha2,6Galbeta1,4Glc, using the ring-opening metathesis polymerization (ROMP). Our synthetic strategy involves the modification of an N-hydroxysuccinimide (NHS) ester-substituted polymer generated by ROMP with the aminopropyl glycoside of the trisaccharide. The conjugation efficiency for the coupling is high; when 0.3 equiv of the trisaccharide derivative were used relative to NHS ester groups, the mole fraction (chi) of trisaccharide ligand incorporated onto the backbone was 0.3. A fluorescein-labeled version of the multivalent ligand binds to cells expressing CD22.
Yang
Zhi-Qiang
ZQ
Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Puffer
Erik B
EB
Pontrello
Jason K
JK
Kiessling
Laura L
LL
D000911:Antibodies, Monoclonal / Q000737:chemistry; D015703:Antigens, CD / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D002240:Carbohydrate Sequence; D015815:Cell Adhesion Molecules; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000378:metabolism; D005434:Flow Cytometry; D019793:Fluorescein / Q000737:chemistry; D006801:Humans; D019169:Jurkat Cells / Q000378:metabolism; D037102:Lectins / Q000378:metabolism*; D008024:Ligands; D016393:Lymphoma, B-Cell / Q000378:metabolism; D008969:Molecular Sequence Data; D010504:Periodic Acid / Q000494:pharmacology; D051918:Sialic Acid Binding Ig-like Lectin 2; D014312:Trisaccharides / Q000138:chemical synthesis* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; D015815:Cell Adhesion Molecules; D018985:Epitopes, B-Lymphocyte; D037102:Lectins; D008024:Ligands; D051918:Sialic Acid Binding Ig-like Lectin 2; D014312:Trisaccharides; D010504:Periodic Acid; C009288:metaperiodate; D019793:Fluorescein