17 6 2005 11 PROGRESS IN CHEMISTRY Vol. 17 No. 6 Nov., 2005 3 ( 266003) 3 3 ( 266042), : Q53 ; O62911 : A : 10052281X(2005) 0621054206 The Bioactivity of Glycocluster and Glycodendrimer Lu Weishen ( Institute of Marine Drugs and Food, Ocean University of China, Qingdao 266003, China) Zhang Xiaoru 3 3 (College of Chemistry and Molecular Engineering, Qingdao University of Science & Technology, Qingdao 266042, China) Abstract A new type of glycoconjugate2glycocluster and glycodendrimer has been designed as mimics for the multivalent effect in nature. The recent advances in bioactivity of glycocluster and glycodendrimer and their potential applications are reviewed in this article. Key words carbohydrate ; glycocluster ; glycodendrimer ; multivalent effect ; bioactivity,,, ( ), 2,, [1 ], ( multivalent effect ) ( cluster effect) [3,4 ], K d mmolπl molπl, ;, 2,,,,, ( glycocluster ) [2 2 ] (glycodendrimer), 1 : 2004 11, : 2005 2 3 (No. 2001CCA01600) 3 3 e2mail :zhangxr7407 @126. com
6 1055 [5, 6 2 3 ] 4 5, 2 200 257 [9 ],,,,, [7 ], 1983 Lee [8 ],,, (2), (HA) 11 (1) (HA), [13 ],, :, (CRD), ;,, [14 16 ] Roy [16 ] PAMAM 6a 6d, ( enzymelinked lectin assay,, ELLA) 2acid Limax flavus, 1,,,, IC 50,, 1 (type 1, fimbriae), Lindhorst [9 12 ] (3), ELISA ( )
1056 17 1 2acid Limax flavus Table 1 Inhibition of Binding of Human 2Acid Glycoprotein to Limax flavus by sialodendrimers compound IC 50 (nmolπl) a relative potency a phenyl 22thio2 2sialoside 242 1 PAMAM2based 4mer 6a 6912 (277) 315 (0187) PAMAM2based 8mer 6b 2115 (172) 11 (114) PAMAM2based 16mer 6c 2189 (46. 2) 84 (512) PAMAM2based 32mer 6d 1113 (36. 2) 210 (617) a : values in parentheses are based on a per sialoside residue SLT2 SLT2,N2, [21 AB 5, ] A 5 B ASGPR 5 B, A [18 ] Gb3[ 2D2Gal (1 4) 2D2Gal (1 4) 2D2Glc (1 O2ceramide) ] Gb3, Gb3, 5, Kitov O157 H7 (SLT2 ) B5, [3,19,20 ], (starfish,7), 30!,, B, SLT2 IC 50 4 10-10, SLT2 IC 50 6 10-9,, 21 N2 ASGPR,,
6 1057, Gal 1 3GalNAc 1, PAMAM( N2 ) T (13a 13d), [22 ] Lee N2 YEE (8), N2 IgG 10 000, [23 ], [24 ] Schuber, ELISA (9) [25 ], IgG T N2, 13a 13b 13c 13d IC 50 510 214 114 016 nmol, 460 (10 12), 960 1 700 3 800 4 32,,, = 2753, 2 292 30 1, G219 [26, ASGPR ] 41 31,, MUC1,,,, (HAR) HAR, Gal,, anti2 Gal,,, anti2 Gal [4 ] ( TACAs) : anti2 Gal Tn ( GalNAc 1 O2SerΠThr), stn (NeuAc 2 2GalOR, 6GalNAc 1 O2SerΠThr ) T ( Gal 1 anti2 Gal, Gal 1 3GalNAc 1 O2SerΠThr) [27 ], [28 3Gal 1 4GlcNAc 1 3Gal 1 4Glc 12 [32,33 ] ( ] ), Gal 1 Tn Tatsushi 3Gal, [27 ] GalNAc 1 O2Ser [34 ], starburst Wang : GalNAc 1 O2,1999 2Gal Ser, pnas( N2 ), starburst 7 ( ), T, [35 ] 14, ( ELISA), C anti2t stn, IC Danishefsky [29 ] 50 = 710nmolΠL,, 718 10 3 stn T,Roy [30,31 ],Wang 2Gal T BSA,,
1058 17, ( 50 625 ), 3 [36 ] [37 ] [38 ] 2Gal, [ 7 ] (Zhang X R), [39,40 ], [41 ],,,, [43 ], 5950,,,, 2,,,, 2004, 22 (5) : 482 486 [27] Toyokuni T, Singhal A K. Chem. Soc. Rev., 1995, 231 242 [ 1 ] ( Ye X S). 21 (The Strategy on [28] Springer G F. Science, 1984, 224 : 1198 1206 Organic Chemistry Development in the 21st Century)., [29] Schwarz J B, Kuduk S D, Danishefsky SJ. J. Am. Chem. Soc.,, (eds. Du C P, Liu L S and Zhang H). : ( Beijing : Chemical Industry Press), 2002. 307 316 [ 2 ] Mammen M, Choi S K, Whitesides G M. Angew. Chem. Int. Ed., 1998, 37 : 2754 2794 [ 3 ] Bertozzi C R, Kiessling L L. Science, 2001, 291 (23) : 2357 2364 [ 4 ] Davis B G. J. Chem. Soc., Perkin Trans. 1, 1999, 3215 3237 [ 5 ] Bezougka K. Reviews in Molecular Biotechnology, 2002, 90 : 269 290 [ 6 ] Gestwicki J E, Cairo C W, Strong L E, et al. J. Am. Chem. Soc., 2002, 124 : 14922 14933 (Li Y X), ( Guan H S). (Chin. J. Org. Chem. ), 2004, 24 (2) : 119 126 [ 8 ] Lee Y C, Towsend R R, Hardy M R, et al. J. Biol. Chem., 1983, 258 : 199 205 [ 9 ] Lindhorst T K, Dubber M, Krallmann2Wenzel U, et al. Eur. J. Org. Chem., 2000, 2027 2034 [10] Kgtter S, Krallmann2Wenzel U, Lindhorst T K, et al. J. Chem. Soc., Perkin Trans. 1, 1998, 2193 2200 [11] Lindhorst T K, Kgtter S, Krallmann2Wenzel U, et al. J. Chem. Soc., Perkin Trans. 1, 2001, 823 831 [12] Ashton P R, Hounsell E F, Jayaraman N, et al. J. Org. Chem., 1998, 63 : 3429 3437 [13] Reuter J D, Myc A, Hayes M M, et al. Bioconjugate Chem., 1999, 10 : 271 278 [14] Furuike T, Aiba S, Suzuki T, et al. J. Chem. Soc., Perkin Trans. 1, 2000, 3000 3005 [15] Zanini D, Roy R. J. Org. Chem., 1996, 61 : 7348 7354 [16] Meunier S J, Wang S N, Roy R. Can. J. Chem., 1997, 75 : 1472 1482 [17] Zanini D, Roy R. J. Org. Chem., 1998, 63 : 3486 3491 [18] Sandvig K, Deurs B. The EMBO Journal, 2000, 19(22) : 5943 [19] Kitov P I, Sadowska J M, Mulvey G, et al. Nature, 2000, 403 : 669 672 [20] Fan E, Zhang Z S, Minke W E. J. Am. Chem. Soc., 2000, 122 : 2663 2664 [21] Rice K G. in Glycosciences : Status and Perspectives (eds. Gabius H J, Gabius S). Weinheim : Chapman & Hall, 1997. 471 483 [22] Lee Y C. Carbohydrate Recognition in Cellular Function ( eds. Bock G, Harnette S). Chichester : Wiley, 1989. 80 95 [23] Ozaki K, Lee R T, Lee Y C, Kawasaki T. Glycoconjuate J., 1995, 12 : 268 274 [24] Hangeland J J, Levis J T, Lee Y C, et al. Bioconjugate Chem., 1995, 6 : 695 701 [25] Kichler A, Schuber F. Glycoconjugate J., 1995, 12 : 275 281 [26] Zhang X R, Li Y X, Chu S D, Guan H S. Chin. J. Chem., 1999, 121 : 2662 2673 [30] Baek M G, Rittenhouse2Olson K, Roy R. Chem. Commun., 2001, 257 258 [31] Roy R, Baek M G. Reviews in Molecular Biotechnology, 2002, 90 : 291 309 [32] Zhu T, Boons G J. J. Chem. Soc., Perkin Trans. 1, 1998, 857 861
6 1059 [33] Fang J W, Li J, Chen X, et al. J. Am. Chem. Soc., 1998, 120 (27) : 6635 6638 [34] Hanessian S, Huynh H K, Reddy G V, et al. Tetrahedron, 2001, 57 : 3281 3290 [35] Wang J Q, Chen X, Wang P G, et al. J. Am. Chem. Soc., 1999, 121 : 8174 8181 [36] Xian M, Fatima Z, Wang P G, et al. J. Comb. Chem., 2004, 6 : 126 134 [37] Zhang W, Wang J Q, Wang G P, et al. J. Carbohydr. Chem., 1999, 18 (8) : 1009 1017 [38] Wang J Q, Zhang B Y, Wang P G, et al. J. Carbohydr. Chem., 2003, 22 (6) : 347 376 [39] (Lu Y P), (Cai M S), (Li Z J). (Acta Chimica Sinica), 2002, 60(2) : 360 366 [40] Lu Y P, Li H, Cai M S, Li Z J. Carbohydrate Research, 2001, 334 : 289 294 [41] (Li Y W). (Ph D Dissertation). (Ocean University of China), 2004 [42] Gestwicki J E, Kiessling L L. Nature, 2002, 415 : 81 84 ( ) Π ( ) ( ) Fischer- Tropsch ( ) 2 ( ) ( ) ( ) ( ) ( ) ( ) ( )