Heterobifunctional multivalent inhibitor-adaptor mediates specific aggregation between Shiga toxin and a pentraxin.
[reaction: see text] The first example of a multivalent heterofunctional inhibitor-adaptor, called "BAIT", is described. This multivalent inhibitor-adaptor is able to capture a "target" receptor (Shiga toxin) through its recognition of one ligand of a heterobivalent headgroup while the other ligand binds to an endogenous "trap" protein (serum amyloid P component, SAP). BAIT showed markedly enhanced inhibition of toxin activity. An efficient synthesis of this multivalent cluster containing heterobifunctional ligands was accomplished by chemical and chemoenzymatic approaches.
Solomon
Dmitry
D
Alberta Ingenuity Centre for Carbohydrate Science, Department of Chemistry, University of Alberta, Edmonton AB, T6G 2G2 Canada.
Kitov
Pavel I
PI
Paszkiewicz
Eugenia
E
Grant
Gordon A
GA
Sadowska
Joanna M
JM
Bundle
David R
DR
D002097:C-Reactive Protein / Q000737:chemistry* / Q000378:metabolism*; D006031:Glycosylation; D008024:Ligands; D015394:Molecular Structure; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism*; D000683:Serum Amyloid P-Component / Q000737:chemistry / Q000378:metabolism; D022621:Shiga Toxin / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D000099153:Pentraxins
D002097:C-Reactive Protein; D008024:Ligands; D009419:Nerve Tissue Proteins; D000683:Serum Amyloid P-Component; D022621:Shiga Toxin; D000099153:Pentraxins