Abstract
Preparation of substituent-diverse, triazole-iduronic acid hybrid molecules by click reaction of an azido iduronic acid derivative with randomly chosen alkynes is described. Library members were screened for their ability to inhibit α-l-iduronidase, and hit molecules and analogues were then investigated for their ability to stabilize rh-α-IDUA in a thermal denaturation study. This work resulted in the discovery of the first small molecules that can be used to stabilize exogenous rh-α-IDUA protein in vitro.
MeSH terms
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Click Chemistry
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Drug Discovery*
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Enzyme Stability / drug effects
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Humans
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Iduronic Acid / chemistry
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Iduronic Acid / pharmacology*
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Iduronidase / antagonists & inhibitors*
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Iduronidase / metabolism
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Molecular Structure
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Mucopolysaccharidosis I / drug therapy*
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Mucopolysaccharidosis I / metabolism
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Small Molecule Libraries / chemical synthesis*
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Small Molecule Libraries / chemistry
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Small Molecule Libraries / pharmacology*
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Triazoles / chemistry
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Triazoles / pharmacology*
Substances
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Small Molecule Libraries
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Triazoles
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Iduronic Acid
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Iduronidase