title: Identification and characterization of a galactosyl peptide mimetic. Implications for use in removing xenoreactive anti-A Gal antibodies.
abstract: Gal alpha 1,3 Gal is thought to be the major antigenic epitope present on pig tissues to which XNAs bind. Removal of antibodies directed against that structure may be critical to the success of pig to human xeno-transplantation. As a first step toward the development of ligands capable of removing XNAs, we have used a phage-displayed peptide library to identify a six-amino-acid peptide that binds to the lectin GS-1-B4 (which binds the carbohydrate Gal alpha 1,3 Gal). This peptide blocks the binding of GS-1-B4 to pig aortic endothelial cells. The carbohydrate Gal alpha 1,3 Gal competes with the binding of GS-1-B4 to the peptide, suggesting that they may bind the same site. Using a RBC agglutination assay, we show that this peptide inhibits the agglutination of pig RBCs by heat-inactivated human serum at concentrations similar to that of Gal alpha 1,3 Gal.
authors.affiliation: Nextran, Princeton, NJ 08536, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Kooyman
authors.forename: S B
authors.initials: SB
authors.lastname: McClellan
authors.forename: W
authors.initials: W
authors.lastname: Parker
authors.forename: P L
authors.initials: PL
authors.lastname: Avissar
authors.forename: M A
authors.initials: MA
authors.lastname: Velardo
authors.forename: J L
authors.initials: JL
authors.lastname: Platt
authors.forename: J S
authors.initials: JS
authors.lastname: Logan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000378:metabolism / Q000494:pharmacology; D001011:Aorta / Q000737:chemistry; D001435:Bacteriophages; D001665:Binding Sites; D001667:Binding, Competitive; D002240:Carbohydrate Sequence; D004187:Disaccharides / Q000276:immunology* / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D004903:Erythrocyte Aggregation / Q000187:drug effects; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism / Q000494:pharmacology; D037102:Lectins / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology*; D013552:Swine
chemical_list: D000906:Antibodies; D004187:Disaccharides; D000939:Epitopes; D007075:Immunoglobulin M; D037102:Lectins; D009842:Oligopeptides; C055075:galactosyl-(1-3)galactose