Synthesis of multivalent Streptococcus suis adhesion inhibitors by enzymatic cleavage of polygalacturonic acid and 'click' conjugation

Hilbert M. Branderhorst; Raymond Kooij; Annika Salminen; Lieneke H. Jongeneel; Christopher J. Arnusch; Rob M. J. Liskamp; Jukka Finne; Roland J. Pieters

doi:10.1039/b800283e

Synthesis of multivalent Streptococcus suis adhesion inhibitors by enzymatic cleavage of polygalacturonic acid and 'click' conjugation

Hilbert M. Branderhorst, Raymond Kooij, Annika Salminen, Lieneke H. Jongeneel, Christopher J. Arnusch, Rob M. J. Liskamp, Jukka Finne, Roland J. Pieters

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

A galabiose disaccharide building block was synthesized by an efficient pectinase cleavage of polygalacturonic acid and subsequent chemical functional group transformations. Besides the disaccharide, the corresponding trisaccharide was also obtained and modified. The compounds were subsequently conjugated to dendrimers with up to eight end groups using 'click' chemistry. The compounds were evaluated as inhibitors of adhesion of the pathogen Streptococcus suis in a hemagglutination assay and strong inhibition was observed for the tetra- and octavalent galabiose compound with MIC values in the low nanomolar range. The corresponding octavalent trisaccharide was a ca. 20-fold weaker inhibitor.

Original language	English
Pages (from-to)	1425-1434
Number of pages	10
Journal	Organic & Biomolecular Chemistry
Volume	6
Issue number	8
DOIs	https://doi.org/10.1039/b800283e
Publication status	Published - 1 Jan 2008

Keywords

4 O alpha D galactopyranosyl D galactose
4-O-alpha-D-galactopyranosyl-D-galactose
dendrimer
disaccharide
pectin
polygalacturonase
polygalacturonic acid
unclassified drug
article
carbohydrate analysis
cell adhesion
chemical structure
chemistry
dose response
drug effect
hemagglutination inhibition test
molecular genetics
pathogenicity
sensitivity and specificity
Streptococcus suis
synthesis

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10.1039/b800283e

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@article{7347db53ddea4d91b75d0bac7708a779,

title = "Synthesis of multivalent Streptococcus suis adhesion inhibitors by enzymatic cleavage of polygalacturonic acid and 'click' conjugation",

abstract = "A galabiose disaccharide building block was synthesized by an efficient pectinase cleavage of polygalacturonic acid and subsequent chemical functional group transformations. Besides the disaccharide, the corresponding trisaccharide was also obtained and modified. The compounds were subsequently conjugated to dendrimers with up to eight end groups using 'click' chemistry. The compounds were evaluated as inhibitors of adhesion of the pathogen Streptococcus suis in a hemagglutination assay and strong inhibition was observed for the tetra- and octavalent galabiose compound with MIC values in the low nanomolar range. The corresponding octavalent trisaccharide was a ca. 20-fold weaker inhibitor. ",

keywords = "4 O alpha D galactopyranosyl D galactose, 4-O-alpha-D-galactopyranosyl-D-galactose, dendrimer, disaccharide, pectin, polygalacturonase, polygalacturonic acid, unclassified drug, article, carbohydrate analysis, cell adhesion, chemical structure, chemistry, dose response, drug effect, hemagglutination inhibition test, molecular genetics, pathogenicity, sensitivity and specificity, Streptococcus suis, synthesis",

author = "Branderhorst, {Hilbert M.} and Raymond Kooij and Annika Salminen and Jongeneel, {Lieneke H.} and Arnusch, {Christopher J.} and Liskamp, {Rob M. J.} and Jukka Finne and Pieters, {Roland J.}",

year = "2008",

month = jan,

day = "1",

doi = "10.1039/b800283e",

language = "English",

volume = "6",

pages = "1425--1434",

journal = "Organic & Biomolecular Chemistry",

issn = "1477-0520",

publisher = "Royal Society of Chemistry",

number = "8",

}

TY - JOUR

T1 - Synthesis of multivalent Streptococcus suis adhesion inhibitors by enzymatic cleavage of polygalacturonic acid and 'click' conjugation

AU - Branderhorst, Hilbert M.

AU - Kooij, Raymond

AU - Salminen, Annika

AU - Jongeneel, Lieneke H.

AU - Arnusch, Christopher J.

AU - Liskamp, Rob M. J.

AU - Finne, Jukka

AU - Pieters, Roland J.

PY - 2008/1/1

Y1 - 2008/1/1

N2 - A galabiose disaccharide building block was synthesized by an efficient pectinase cleavage of polygalacturonic acid and subsequent chemical functional group transformations. Besides the disaccharide, the corresponding trisaccharide was also obtained and modified. The compounds were subsequently conjugated to dendrimers with up to eight end groups using 'click' chemistry. The compounds were evaluated as inhibitors of adhesion of the pathogen Streptococcus suis in a hemagglutination assay and strong inhibition was observed for the tetra- and octavalent galabiose compound with MIC values in the low nanomolar range. The corresponding octavalent trisaccharide was a ca. 20-fold weaker inhibitor.

AB - A galabiose disaccharide building block was synthesized by an efficient pectinase cleavage of polygalacturonic acid and subsequent chemical functional group transformations. Besides the disaccharide, the corresponding trisaccharide was also obtained and modified. The compounds were subsequently conjugated to dendrimers with up to eight end groups using 'click' chemistry. The compounds were evaluated as inhibitors of adhesion of the pathogen Streptococcus suis in a hemagglutination assay and strong inhibition was observed for the tetra- and octavalent galabiose compound with MIC values in the low nanomolar range. The corresponding octavalent trisaccharide was a ca. 20-fold weaker inhibitor.

KW - 4 O alpha D galactopyranosyl D galactose

KW - 4-O-alpha-D-galactopyranosyl-D-galactose

KW - dendrimer

KW - disaccharide

KW - pectin

KW - polygalacturonase

KW - polygalacturonic acid

KW - unclassified drug

KW - article

KW - carbohydrate analysis

KW - cell adhesion

KW - chemical structure

KW - chemistry

KW - dose response

KW - drug effect

KW - hemagglutination inhibition test

KW - molecular genetics

KW - pathogenicity

KW - sensitivity and specificity

KW - Streptococcus suis

KW - synthesis

U2 - 10.1039/b800283e

DO - 10.1039/b800283e

M3 - Article

SN - 1477-0520

VL - 6

SP - 1425

EP - 1434

JO - Organic & Biomolecular Chemistry

JF - Organic & Biomolecular Chemistry

IS - 8

ER -

Synthesis of multivalent Streptococcus suis adhesion inhibitors by enzymatic cleavage of polygalacturonic acid and 'click' conjugation

Abstract

Keywords

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