Synthesis of galabiose-chitosan conjugate as potent inhibitor of Streptococcus suis adhesion.
The aim of this work is to construct a safe and effective drug candidate against Streptococcus suis infection. A panel of chitosan-based polymer conjugates with branched galabiose (Galalpha1-4Gal) side chains was synthesized as inhibitors of S. suis adhesion. The synthesis was achieved by using an aldehyde-functionalized galabiose derivative to graft it onto chitosan amino groups. Structural compositions of the conjugates were verified by 1H NMR spectroscopy and CHN elemental analyses. Potent inhibitory activities of the conjugates against S. suis adhesion to human erythrocytes were determined at low nanomolar concentration by HAI assay. An SPR study revealed a high affinity binding (Kd=39.6 nM) of the conjugate with BSI-B4 lectin. By using biocompatible chitosan as the scaffold for presenting S. suis -specific galabiose units, as well as the concise route tailored for the conjugate syntheses, the present study provides a practical way for explorations of new anti- S. suis therapies.
Xu
Yaozu
Y
Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, China.
Fan
Hongjie
H
Lu
Chengping
C
Gao
George F
GF
Li
Xuebing
X
D000447:Aldehydes / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D001422:Bacterial Adhesion / Q000187:drug effects*; D048271:Chitosan / Q000737:chemistry* / Q000494:pharmacology; D004187:Disaccharides / Q000737:chemistry* / Q000494:pharmacology; D004912:Erythrocytes / Q000382:microbiology; D006801:Humans; D015394:Molecular Structure; D013290:Streptococcal Infections / Q000188:drug therapy*; D017011:Streptococcus suis / Q000187:drug effects*
D000447:Aldehydes; D000588:Amines; D000900:Anti-Bacterial Agents; D004187:Disaccharides; C032103:4-O-alpha-D-galactopyranosyl-D-galactose; D048271:Chitosan