title: Large cyclic peptides as cores of multivalent ligands: application to inhibitors of receptor binding by cholera toxin.
abstract: Large cyclic decapeptides (up to 50-atom ring) were synthesized efficiently on the solid phase with allyl-ester protection of the carboxyl terminus during elongation. Pentavalent ligands, in a "core-linker-finger" modular setup, were assembled by using these cyclic peptide cores to demonstrate large affinity gains for inhibition of surface receptor binding by the cholera toxin B pentamer. The results suggest that the peptide cores retain expanded conformation in solution so that shorter flexible linkers are needed for larger peptide cores to achieve the best inhibitory results.
authors.affiliation: Biomolecular Structure Center, Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Zhongsheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jiyun
authors.initials: J
authors.lastname: Liu
authors.forename: Christophe L M J
authors.initials: CL
authors.lastname: Verlinde
authors.forename: Wim G J
authors.initials: WG
authors.lastname: Hol
authors.forename: Erkang
authors.initials: E
authors.lastname: Fan
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002772:Cholera Toxin / Q000037:antagonists & inhibitors*; D003198:Computer Simulation; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D008024:Ligands; D010456:Peptides, Cyclic; D011956:Receptors, Cell Surface; D002772:Cholera Toxin