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PDBsum entry 1rf2
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References listed in PDB file
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Key reference
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Title
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Nonspanning bivalent ligands as improved surface receptor binding inhibitors of the cholera toxin b pentamer.
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Authors
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J.C.Pickens,
D.D.Mitchell,
J.Liu,
X.Tan,
Z.Zhang,
C.L.Verlinde,
W.G.Hol,
E.Fan.
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Ref.
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Chem Biol, 2004,
11,
1205-1215.
[DOI no: ]
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PubMed id
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Abstract
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A series of bivalent ligands of varying length were synthesized to inhibit the
receptor-binding process of cholera toxin. Competitive surface receptor binding
assays showed that significant potency gains relative to the constituent
monovalent ligands were achieved independently from the ability of the extended
bivalent ligands to span binding sites within the toxin pentamer. Several models
that could account for the unexpected improvement in IC(50) values are examined,
taking into account crystallographic analysis of each ligand in complex with the
toxin pentamer. Evidence is presented that steric blocking at the receptor
binding surface may play a role. The results of our study suggest that the use
of relatively short, "nonspanning" bivalent ligands, or monovalent
ligands of similar topology and bulk may be an effective way of blocking the
interaction of multimeric proteins with their cell surface receptors.
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Figure 1.
Figure 1. Previously Studied Monovalent Ligands to CT and
LT and Chemical Structure of Newly Synthesized Bivalent Ligands
BV1–BV4
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Figure 5.
Figure 5. Electron Density and Fitted Model(A) Electron
density and model for BV1 in complex with CTB[5]. Electron
density is contoured at 2σ in a σ[A]-weighted (mFo–DFc)
difference map.(B) Electron density and model for BV4 in complex
with CTB[5]. Electron density is contoured at 3σ in a
σ[A]-weighted (mFo-DFc) difference map.
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The above figures are
reprinted
by permission from Cell Press:
Chem Biol
(2004,
11,
1205-1215)
copyright 2004.
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