Interference with lectin binding and bacterial adhesion by multivalent carbohydrates and peptidic carbohydrate mimics

被引:40
作者
Pieters, RJ [1 ]
机构
[1] Univ Utrecht, Inst Pharmaceut Sci, Dept Med Chem, NL-3508 TB Utrecht, Netherlands
关键词
multivalent carbohydrates; glycodendrimers; galectins; anti-adhesion; carbohydrate mimicry;
D O I
10.4052/tigg.16.243
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Considering the importance of protein-carbohydrate interactions in biological processes, effective interference with these interactions may prove to be a powerful way towards novel therapeutics. Multivalency is an important principle that characterizes these interactions and is likely a required design principle for the synthesis of molecules with the goal to interfere effectively. Glycodendrimer synthesis is described here along with interference with animal, plant and bacterial lectins. Large affinity enhancements due to multivalency were observed in selected cases. Initial studies with peptide sequences as interfering moieties in protein carbohydrate interactions are also described which yield ligands in the milimolar range.
引用
收藏
页码:243 / 254
页数:12
相关论文
共 50 条
[1]  
André S, 2001, CHEMBIOCHEM, V2, P822, DOI 10.1002/1439-7633(20011105)2:11<822::AID-CBIC822>3.0.CO
[2]  
2-W
[3]   Interference of the galactose-dependent binding of lectins by novel pentapeptide ligands [J].
Arnusch, CJ ;
André, S ;
Valentini, P ;
Lensch, M ;
Russwurm, R ;
Siebert, HC ;
Fischer, MJE ;
Gabius, HJ ;
Pieters, RJ .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (06) :1437-1440
[4]   Adhesion inhibition of F1C-fimbriated Escherichia coli and Pseudomonas aeruginosa PAK and PAO by multivalent carbohydrate ligands [J].
Autar, R ;
Khan, AS ;
Schad, M ;
Hacker, J ;
Liskamp, RMJ ;
Pieters, RJ .
CHEMBIOCHEM, 2003, 4 (12) :1317-1325
[5]   The new antibiotics [J].
Breithaupt, H .
NATURE BIOTECHNOLOGY, 1999, 17 (12) :1165-1169
[6]  
Brouwer AJ, 2001, EUR J ORG CHEM, V2001, P1903
[7]   Synergistic formation of soluble lectin clusters by a templated multivalent saccharide ligand [J].
Burke, SD ;
Zhao, Q ;
Schuster, MC ;
Kiessling, LL .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2000, 122 (18) :4518-4519
[8]   Biological applications of dendrimers [J].
Cloninger, MJ .
CURRENT OPINION IN CHEMICAL BIOLOGY, 2002, 6 (06) :742-748
[9]   High-affinity pentavalent ligands of Escherichia coli heat-labile enterotoxin by modular structure-based design [J].
Fan, EK ;
Zhang, ZS ;
Minke, WE ;
Hou, Z ;
Verlinde, CLMJ ;
Hol, WGJ .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2000, 122 (11) :2663-2664
[10]   Comparative cross-linking activities of lactose-specific plant and animal lectins and a natural lactose-binding immunoglobulin G fraction from human serum with asialofetuin [J].
Gupta, D ;
Kaltner, H ;
Dong, X ;
Gabius, HJ ;
Brewer, CF .
GLYCOBIOLOGY, 1996, 6 (08) :843-849