Multivalent carbohydrate recognition on a glycodendrimer-functionalized flow-through chip

被引:76
作者
Branderhorst, Hilbert M. [1 ]
Ruijtenbeek, Rob [2 ]
Liskamp, Rob M. J. [1 ]
Pieters, Roland J. [1 ]
机构
[1] Univ Utrecht, Dept Med Chem & Chem Biol, Utrecht Inst Pharmaceut Sci, NL-3508 TB Utrecht, Netherlands
[2] Pamgene Int BV, NL-5200 BJ sHertogenbosch, Netherlands
关键词
carbohydrates; glycodendrimers; inhibitors; lectins; microarrays; multivalency;
D O I
10.1002/cbic.200800195
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
Dendrimers were fitted out with up to eight mannose moieties by "click" chemistry. They were subsequently attached to aluminum oxide chips via a spacer that was linked to the dendrimer core; this resulted in a microarroy of glycodendrimers. Binding of the glycodendrimers to the fluorescent lectins ConA and GNA was observable in real time. In a single experiment it was possible to observe the multivalency enhancement or cluster effect in the binding event. This effect was small for ConA, in agreement with its widely spaced binding sites, whereas it was large for GNA with its twelve much more closely spaced binding sites. The dendrimer-fitted chip represents a valuable screening tool for multivalency effects. Furthermore kinetic and thermodynamic data on binding events can be deduced. Inhibition experiments are also possible with the system as was shown for ConA with a-methyl mannose as the inhibitor.
引用
收藏
页码:1836 / 1844
页数:9
相关论文
共 81 条
[1]   Oligosaccharide and glycoprotein Microarrays as tools in HIV glycobiology: Glycan-dependent gp120/protein interactions [J].
Adams, EW ;
Ratner, DM ;
Bokesch, HR ;
McMahon, JB ;
O'Keefe, BR ;
Seeberger, PH .
CHEMISTRY & BIOLOGY, 2004, 11 (06) :875-881
[2]   Novel multivalent mannose compounds and their inhibition of the adhesion of type 1 fimbriated uropathogenic E. coli [J].
Appeldoorn, CCM ;
Joosten, JAF ;
el Maate, FA ;
Dobrindt, U ;
Hacker, J ;
Liskamp, RMJ ;
Khan, AS ;
Pieters, RJ .
TETRAHEDRON-ASYMMETRY, 2005, 16 (02) :361-372
[3]   Synthesis and cholera toxin binding properties of multivalent GM1 mimics [J].
Arosio, D ;
Vrasidas, I ;
Valentini, P ;
Liskamp, RMJ ;
Pieters, RJ ;
Bernardi, A .
ORGANIC & BIOMOLECULAR CHEMISTRY, 2004, 2 (14) :2113-2124
[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]   Strong inhibition of cholera toxin binding by galactose dendrimers [J].
Branderhorst, Hilbert M. ;
Liskamp, Rob M. J. ;
Visser, Gerben M. ;
Pieters, Roland J. .
CHEMICAL COMMUNICATIONS, 2007, (47) :5043-5045
[6]  
Brouwer AJ, 2001, EUR J ORG CHEM, V2001, P1903
[7]   Biological applications of dendrimers [J].
Cloninger, MJ .
CURRENT OPINION IN CHEMICAL BIOLOGY, 2002, 6 (06) :742-748
[8]   A comparison of biological and calorimetric analyses of multivalent glycodendrimer ligands for concanavalin A [J].
Corbell, JB ;
Lundquist, JJ ;
Toone, EJ .
TETRAHEDRON-ASYMMETRY, 2000, 11 (01) :95-111
[9]   Binding studies of α-GaINAc-specific lectins to the α-GaINAc (Tn-antigen) form of porcine submaxillary mucin and its smaller fragments [J].
Dam, Tarun K. ;
Gerken, Thomas A. ;
Cavada, Benildo S. ;
Nascimento, Kyria S. ;
Moura, Tales R. ;
Brewer, C. Fred .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (38) :28256-28263
[10]   Binding of multivalent carbohydrates to concanavalin A and Dioclea grandiflora lectin -: Thermodynamic analysis of the "multivalency effect" [J].
Dam, TK ;
Roy, R ;
Das, SK ;
Oscarson, S ;
Brewer, CF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (19) :14223-14230