Large cyclic peptides as cores of multivalent ligands: application to inhibitors of receptor binding by cholera toxin.
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.
Zhang
Zhongsheng
Z
Biomolecular Structure Center, Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Liu
Jiyun
J
Verlinde
Christophe L M J
CL
Hol
Wim G J
WG
Fan
Erkang
E
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
D008024:Ligands; D010456:Peptides, Cyclic; D011956:Receptors, Cell Surface; D002772:Cholera Toxin