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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 ; 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
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
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
2018-02-18 22:40:08
@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},
  keyword      = {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},
  volume       = {13},
  year         = {2018},
}