A comparison of biological and calorimetric analyses of multivalent glycodendrimer ligands for concanavalin A

被引:105
作者
Corbell, JB
Lundquist, JJ
Toone, EJ [1 ]
机构
[1] Duke Univ, Dept Biochem, Durham, NC 27708 USA
[2] Duke Univ, Dept Chem, Durham, NC 27708 USA
关键词
D O I
10.1016/S0957-4166(99)00589-3
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
The cluster glycoside effect - the observation that multivalent glycosides bind to their polyvalent protein receptors with apparent affinities greater than those that can be rationalized solely on the basis of valency is by now a well established phenomenon. As part of a continuing effort to provide a molecular basis for the cluster glycoside effect, we report here the synthesis of two series of mannosylated dendritic ligands and their performance in a range of competitive and non-competitive binding assays, including hemeagglutination inhibition (HIA), enzyme-linked lectin assays (ELLA) and isothermal titration microcalorimetry (ITC). The first series of ligands contained a semi-rigid glycylglycine spacer and showed no significant performance enhancement in any binding studies. The second series of ligands contained a flexible tetraethylene glycol spacer; these ligands showed marked enhancements at tetravalent and hexavalent levels in both HIA (IC50=3 and <0.8 mu M, respectively) and ITC (K-A=6.2x10(4) and 1.5x10(6) M-1, respectively) studies. In all cases, the thermodynamic parameters of association are consistent with non-specific aggregation rather than enhanced lectin-ligand affinity. This conclusion is reinforced by the lack of enhancements in ligand activity observed in ELLA studies. (C) 2000 Elsevier Science I;td. All rights reserved.
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页码:95 / 111
页数:17
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共 51 条
  • [1] Competitive binding of drugs to the multiple binding sites on human serum albumin. A calorimetric study
    Aki, H
    Goto, M
    Kai, M
    Yamamoto, M
    [J]. JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY, 1999, 57 (01): : 361 - 370
  • [2] SOLUTION PROPERTIES OF OCTYL-BETA-D-GLUCOSIDE .2. THERMODYNAMICS OF MICELLE FORMATION
    ANTONELLI, ML
    BONICELLI, MG
    CECCARONI, G
    LAMESA, C
    SESTA, B
    [J]. COLLOID AND POLYMER SCIENCE, 1994, 272 (06) : 704 - 711
  • [3] Synthetic carbohydrate dendrimers .1. A convergent synthesis of carbohydrate-containing dendrimers
    Ashton, PR
    Boyd, SE
    Brown, CL
    Jayaraman, N
    Nepogodiev, SA
    Stoddart, JF
    [J]. CHEMISTRY-A EUROPEAN JOURNAL, 1996, 2 (09) : 1115 - 1128
  • [4] Lysine-based cluster mannosides that inhibit ligand binding to the human mannose receptor at nanomolar concentration
    Biessen, EAL
    Noorman, F
    vanTeijlingen, ME
    Kuiper, J
    BarrettBergshoeff, M
    Bijsterbosch, MK
    Rijken, DC
    vanBerkel, TJC
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (45) : 28024 - 28030
  • [6] CALORIMETRIC ANALYSIS OF THE BINDING OF LECTINS WITH OVERLAPPING CARBOHYDRATE-BINDING LIGAND SPECIFICITIES
    CHERVENAK, MC
    TOONE, EJ
    [J]. BIOCHEMISTRY, 1995, 34 (16) : 5685 - 5695
  • [7] Monomeric inhibitors of influenza neuraminidase enhance the hemagglutination inhibition activities of polyacrylamides presenting multiple C-sialoside groups
    Choi, SK
    Mammen, M
    Whitesides, GM
    [J]. CHEMISTRY & BIOLOGY, 1996, 3 (02): : 97 - 104
  • [8] On the meaning of affinity: Cluster glycoside effects and concanavalin A
    Dimick, SM
    Powell, SC
    McMahon, SA
    Moothoo, DN
    Naismith, JH
    Toone, EJ
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1999, 121 (44) : 10286 - 10296
  • [9] COLORIMETRIC METHOD FOR DETERMINATION OF SUGARS AND RELATED SUBSTANCES
    DUBOIS, M
    GILLES, KA
    HAMILTON, JK
    REBERS, PA
    SMITH, F
    [J]. ANALYTICAL CHEMISTRY, 1956, 28 (03) : 350 - 356
  • [10] SPECTROSCOPIC DETERMINATION OF TRYPTOPHAN AND TYROSINE IN PROTEINS
    EDELHOCH, H
    [J]. BIOCHEMISTRY, 1967, 6 (07) : 1948 - &