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PDBsum entry 1oda
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Lectin/immune system
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PDB id
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1oda
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structure-Guided design of sialic acid-Based siglec inhibitors and crystallographic analysis in complex with sialoadhesin.
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Authors
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N.R.Zaccai,
K.Maenaka,
T.Maenaka,
P.R.Crocker,
R.Brossmer,
S.Kelm,
E.Y.Jones.
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Ref.
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Structure, 2003,
11,
557-567.
[DOI no: ]
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PubMed id
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Abstract
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The Siglec family of receptors mediates cell surface interactions through
recognition of sialylated glycoconjugates. The crystal structure of the
N-terminal immunoglobulin-like domain of the Siglec sialoadhesin (SnD1) in
complex with 2,3-sialyllactose has informed the design of sialic acid analogs
(sialosides) that bind Siglecs with significantly enhanced affinities and
specificities. Binding assays against sialoadhesin (Sn; Siglec-1), CD22
(Siglec-2), and MAG (Siglec-4) show a 10- to 300-fold reduction in IC(50) values
(relative to methyl-alpha-Neu5Ac) for three sialosides bearing aromatic group
modifications of the glycerol side chain:
Me-alpha-9-N-benzoyl-amino-9-deoxy-Neu5Ac (BENZ),
Me-alpha-9-N-(naphthyl-2-carbonyl)-amino-9-deoxy-Neu5Ac (NAP), and
Me-alpha-9-N-(biphenyl-4-carbonyl)-amino-9-deoxy-Neu5Ac (BIP). Crystal
structures of these sialosides in complex with SnD1 suggest explanations for the
differences in specificity and affinity, providing further ideas for compound
design of physiological and potentially therapeutic relevance.
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Figure 1.
Figure 1. Chemical Structures of Sialosides Used in This
Study
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2003,
11,
557-567)
copyright 2003.
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