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Monosaccharide Derivatives with Low-Nanomolar Lectin Affinity and High Selectivity Based on Combined Fluorine-Amide, Phenyl-Arginine, Sulfur-π, and Halogen Bond Interactions

Zetterberg, Fredrik R. ; Peterson, Kristoffer LU ; Johnsson, Richard E. LU ; Brimert, Thomas ; Håkansson, Maria LU ; Logan, Derek T. LU orcid ; Leffler, Hakon LU and Nilsson, Ulf J. LU (2018) In ChemMedChem 13(2). p.133-137
Abstract

The design of small and high-affinity lectin inhibitors remains a major challenge because the natural ligand binding sites of lectin are often shallow and have polar character. Herein we report that derivatizing galactose with un-natural structural elements that form multiple non-natural lectin-ligand interactions (orthogonal multipolar fluorine-amide, phenyl-arginine, sulfur-π, and halogen bond) can provide inhibitors with extraordinary affinity (low nanomolar) for the model lectin, galectin-3, which is more than five orders of magnitude higher than the parent galactose; moreover, is selective over other galectins.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Fluorine multipolar interactions, Galectin-3, Halogen bonds, Inhibitors, Lectins, Sulfur-π
in
ChemMedChem
volume
13
issue
2
pages
133 - 137
publisher
Wiley-Blackwell
external identifiers
  • scopus:85040694778
  • pmid:29194992
ISSN
1860-7179
DOI
10.1002/cmdc.201700744
language
English
LU publication?
yes
id
32189061-b29f-4229-a66c-985a0965c316
date added to LUP
2018-01-30 14:02:33
date last changed
2024-01-29 10:53:35
@article{32189061-b29f-4229-a66c-985a0965c316,
  abstract     = {{<p>The design of small and high-affinity lectin inhibitors remains a major challenge because the natural ligand binding sites of lectin are often shallow and have polar character. Herein we report that derivatizing galactose with un-natural structural elements that form multiple non-natural lectin-ligand interactions (orthogonal multipolar fluorine-amide, phenyl-arginine, sulfur-π, and halogen bond) can provide inhibitors with extraordinary affinity (low nanomolar) for the model lectin, galectin-3, which is more than five orders of magnitude higher than the parent galactose; moreover, is selective over other galectins.</p>}},
  author       = {{Zetterberg, Fredrik R. and Peterson, Kristoffer and Johnsson, Richard E. and Brimert, Thomas and Håkansson, Maria and Logan, Derek T. and Leffler, Hakon and Nilsson, Ulf J.}},
  issn         = {{1860-7179}},
  keywords     = {{Fluorine multipolar interactions; Galectin-3; Halogen bonds; Inhibitors; Lectins; Sulfur-π}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{2}},
  pages        = {{133--137}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{ChemMedChem}},
  title        = {{Monosaccharide Derivatives with Low-Nanomolar Lectin Affinity and High Selectivity Based on Combined Fluorine-Amide, Phenyl-Arginine, Sulfur-π, and Halogen Bond Interactions}},
  url          = {{http://dx.doi.org/10.1002/cmdc.201700744}},
  doi          = {{10.1002/cmdc.201700744}},
  volume       = {{13}},
  year         = {{2018}},
}