Abstract
A polymer based dynamic combinatorial library (DCL) was generated through condensation between aldehyde functionalized linear poly(glycidol) (APG) and galactose containing acylhydrazide derivatives. Pentameric E. coli heat labile enterotoxin B subunit (LTB) was subsequently applied to the DCL as external stimulus, resulting in amplification of a specific acylhydrazone side chain that was further used for the synthesis of a multivalent LTB inhibitor. In the in vitro biological evaluation, this inhibitor exhibited strong inhibition properties as well as low cytotoxicity.
Keywords:
Dynamic combinatorial chemistry; E. coli heat labile toxin; Multivalent interaction; Protein inhibition; Supramolecular chemistry.
Copyright © 2020 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aldehydes / chemistry
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Aldehydes / pharmacology*
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Bacterial Toxins / antagonists & inhibitors*
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Bacterial Toxins / metabolism
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Cell Line
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Cell Survival / drug effects
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Combinatorial Chemistry Techniques*
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Dose-Response Relationship, Drug
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Enterotoxins / antagonists & inhibitors*
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Enterotoxins / metabolism
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Escherichia coli Proteins / antagonists & inhibitors*
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Escherichia coli Proteins / metabolism
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Galactose / chemistry
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Galactose / pharmacology*
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Humans
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Hydrazines / chemistry
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Hydrazines / pharmacology*
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Molecular Structure
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Propylene Glycols / chemistry
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Propylene Glycols / pharmacology*
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Structure-Activity Relationship
Substances
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Aldehydes
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Bacterial Toxins
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Enterotoxins
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Escherichia coli Proteins
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Hydrazines
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Propylene Glycols
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polyglycidol
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heat-labile enterotoxin, E coli
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Galactose