Inhibition of Streptococcus suis adhesion by dendritic galabiose compounds at low nanomolar concentration.
A series of mono-, di-, and tetravalent galabiose (Galalpha1-4Gal) compounds were synthesized in good yields by coupling of a general carboxylic acid-bearing sugar building block to dendritic scaffolds based on the 3,5-di-(2-aminoethoxy)benzoic acid branching unit. Furthermore, a poly(amidoamine)- (PAMAM-) based dendritic galabioside was synthesized containing eight galabiose units. All galabiosides were tested in a hemagglutination assay and a surface plasmon resonance (SPR) competition assay in order to establish their potency in the binding to the bacterial Gram-positive pathogen Streptococcus suis. A monovalent galabioside containing a short spacer was used as a reference compound in all the assays. Variations in the scaffold as well as in the spacer arms were introduced to determine their influence on the inhibition. The best inhibitor of hemagglutination was an octavalent galabioside with a minimal inhibitory concentration (MIC) of 0.3 nM, to the best of our knowledge the first example of inhibition of bacterial binding by a soluble carbohydrate at a subnanomolar concentration.
Joosten
John A F
JA
Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Post Office Box 80082, NL-3508 TB Utrecht, The Netherlands.
Loimaranta
Vuokko
V
Appeldoorn
Chantal C M
CC
Haataja
Sauli
S
El Maate
Fatna Ait
FA
Liskamp
Rob M J
RM
Finne
Jukka
J
Pieters
Roland J
RJ
D001422:Bacterial Adhesion / Q000187:drug effects; D004187:Disaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000382:microbiology / Q000502:physiology; D006386:Hemagglutination Tests; D006801:Humans; D008826:Microbial Sensitivity Tests; D010059:Ovomucin / Q000737:chemistry; D017011:Streptococcus suis / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance
D004187:Disaccharides; C032103:4-O-alpha-D-galactopyranosyl-D-galactose; D010059:Ovomucin