Multimeric Lactoside "Click Clusters" as Tools to Investigate the Effect of Linker Length in Specific Interactions with Peanut Lectin, Galectin-1, and-3
(2010) In ChemBioChem 11(10). p.1430-1442- Abstract
- Multimeric lactosides based on carbohydrate scaffolds with valencies ranging from 1 to 4 and different linker lengths were synthesized by a copper-catalyzed azide-alkyne cycloaddition (CuAAC). The binding affinities and crosslinking abilities of the new "click clusters" toward biologically relevant galectins (gal-1, gal-3) and peanut lectin were evaluated by fluorescent polarization assay (FPA) and enzyme-linked lectin assay (ELLA), respectively. FPA indicated that the binding affinities of the synthetic multilactosides towards the galectins increased proportionally with their lactosyl content, without significant differences due to the spacer length. ELLA evidenced a modest cluster effect for the multivalent conjugates, with a relative... (More)
- Multimeric lactosides based on carbohydrate scaffolds with valencies ranging from 1 to 4 and different linker lengths were synthesized by a copper-catalyzed azide-alkyne cycloaddition (CuAAC). The binding affinities and crosslinking abilities of the new "click clusters" toward biologically relevant galectins (gal-1, gal-3) and peanut lectin were evaluated by fluorescent polarization assay (FPA) and enzyme-linked lectin assay (ELLA), respectively. FPA indicated that the binding affinities of the synthetic multilactosides towards the galectins increased proportionally with their lactosyl content, without significant differences due to the spacer length. ELLA evidenced a modest cluster effect for the multivalent conjugates, with a relative potency per lactoside ranging from 2.1 to 3.2. Nearly identical binding affinities were recorded for derivatives differing in the length of the linkers, in agreement with the FPA data. These results demonstrate that this parameter does not significantly influence the recognition process when interactions occur at a single lectin site. Molecular dynamics revealed that glycoconjugates adopt a pseudoglobular structure with a random localization of the lactoside residues. These spatial distributions were observed irrespective of the linker length; this explains the virtually equal affinities recorded by ELLA. In contrast, two-site "sandwich" ELLA clearly revealed that multivalent derivatives bearing the longest spacers were more efficient for crosslinking lectins. Intrinsic affinities, devoid of aggregation effects, and crosslinking capabilities are, therefore, not directly related phenomena that must be taking into consideration in neoglycoconjugate design for specific applications. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1676868
- author
- Gouin, Sebastien G. ; Garcia Fernandez, Jose Manuel ; Vanquelef, Enguerran ; Dupradeau, Francois-Yves ; Salomonsson, Emma LU ; Leffler, Hakon LU ; Ortega-Munoz, Mariano ; Nilsson, Ulf LU and Kovensky, Jose
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- molecular dynamics, linkers, lectins, carbohydrates, click chemistry
- in
- ChemBioChem
- volume
- 11
- issue
- 10
- pages
- 1430 - 1442
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000280787400018
- scopus:77954373398
- pmid:20549756
- ISSN
- 1439-4227
- DOI
- 10.1002/cbic.201000167
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240), Division of Microbiology, Immunology and Glycobiology - MIG (013025200)
- id
- 0833e1f7-b5f4-43ad-b3ef-427916898a7f (old id 1676868)
- date added to LUP
- 2016-04-01 10:17:00
- date last changed
- 2022-02-10 00:36:43
@article{0833e1f7-b5f4-43ad-b3ef-427916898a7f,
abstract = {{Multimeric lactosides based on carbohydrate scaffolds with valencies ranging from 1 to 4 and different linker lengths were synthesized by a copper-catalyzed azide-alkyne cycloaddition (CuAAC). The binding affinities and crosslinking abilities of the new "click clusters" toward biologically relevant galectins (gal-1, gal-3) and peanut lectin were evaluated by fluorescent polarization assay (FPA) and enzyme-linked lectin assay (ELLA), respectively. FPA indicated that the binding affinities of the synthetic multilactosides towards the galectins increased proportionally with their lactosyl content, without significant differences due to the spacer length. ELLA evidenced a modest cluster effect for the multivalent conjugates, with a relative potency per lactoside ranging from 2.1 to 3.2. Nearly identical binding affinities were recorded for derivatives differing in the length of the linkers, in agreement with the FPA data. These results demonstrate that this parameter does not significantly influence the recognition process when interactions occur at a single lectin site. Molecular dynamics revealed that glycoconjugates adopt a pseudoglobular structure with a random localization of the lactoside residues. These spatial distributions were observed irrespective of the linker length; this explains the virtually equal affinities recorded by ELLA. In contrast, two-site "sandwich" ELLA clearly revealed that multivalent derivatives bearing the longest spacers were more efficient for crosslinking lectins. Intrinsic affinities, devoid of aggregation effects, and crosslinking capabilities are, therefore, not directly related phenomena that must be taking into consideration in neoglycoconjugate design for specific applications.}},
author = {{Gouin, Sebastien G. and Garcia Fernandez, Jose Manuel and Vanquelef, Enguerran and Dupradeau, Francois-Yves and Salomonsson, Emma and Leffler, Hakon and Ortega-Munoz, Mariano and Nilsson, Ulf and Kovensky, Jose}},
issn = {{1439-4227}},
keywords = {{molecular dynamics; linkers; lectins; carbohydrates; click chemistry}},
language = {{eng}},
number = {{10}},
pages = {{1430--1442}},
publisher = {{John Wiley & Sons Inc.}},
series = {{ChemBioChem}},
title = {{Multimeric Lactoside "Click Clusters" as Tools to Investigate the Effect of Linker Length in Specific Interactions with Peanut Lectin, Galectin-1, and-3}},
url = {{http://dx.doi.org/10.1002/cbic.201000167}},
doi = {{10.1002/cbic.201000167}},
volume = {{11}},
year = {{2010}},
}