在哺乳類動物的腫瘤細胞表面都會暴露出大量不同於一般正常細胞的醣體，因此我們希望能藉由將本實驗室之前所研究的碳水化合物腫瘤抗體如結腸癌中的Tn引進SELEX（Systemic Evolution of Ligands by EXponential Enrichments）系統來開發出對此類不正常醣體具有高度辨識能力的aptamers（經過SELEX系統所篩選出對特定化合物具有強作用力之單股去氧核醣核酸），希望能以此來開發針對不正常醣體具有高度專一性之生物偵測器，將此利用在醫療的診斷上，期望可達到在癌症發生初期時即可偵測出病變的診斷工具。

Cell surface carbohydrates have been shown to play essential biological roles in divers biological phenomena such as molecular recognition, used the carbohydrate antigen （ex. Tn antigen found in gastrointestinal tissues） to distinguish cancer cell with normal cell. Then used Tn antigen as target molecular in the SELEX（Systemic Evolution of Ligands by EXponential Enrichments）, found the aptamers（isolation of DNA ligands out of the random sequence pool）. The aptamers have high affinity and selectivity to Tn antigen. The aptamers can be applied to develop sensor for Tn antigen. We wish the sensor could be used to diagnostic cancer early.

參考文獻：
1 (a) Koganty, R. R.; Reddish, M. A. and
Longenecker, B. M. Drug Discovery
Today 1996, 1, 190. (b) Fung, P. Y. S.;
Madej, M.; Koganty, R. R.;
Longenecker, B. M. Cancer Res. 1990, 50,
4308. (c) MacLean, G. D.; Bowen-
Yacashin, M. B.; Samuel, J.; Meikle, A.;
Sturat, G.; Nation, J.; Poppema,
S.; Jerry, M.; Koganty, R. R.; Wong, T.;
Longenecker, B. M. Cancer Immunol.
Immunther. 1992. 11, 292. (d) MacLean, G. D.;
Redish, M.; Koganty, R. R.;
Wong, T.; Hanhi, S.; Smolenski, M.; Samuel,
J.; Nabholtz, J. M.;
Longenecker, B. M. Cancer Immunol.
Immunother. 1993, 36, 215. (e)
Longenecker, B. M.; MacLean, G. D. The
Immunologist 1993, 1, 89.
2 (a) Mahal, L. K.; Yarema, K. J.; Bertozzi, C.
R. Science 1997, 276, 1125.
(b) Lemieux, G. A.; Bertozzi, C. R. Chem.
Biol. 2001, 8, 265.
3 Handall, R. L.; Chappell, M. D.
Glycochemistry: Principles, Synthesis,
and Application Wang, P. G.; Bertozzi, C. R.
Ed. Marcel dekker, Inc.,
NEW YORK, 2001, pp. 177-220.
4 Tomas, D. B.; Winzler, R. J. J. Biol. Chem.
1969, 244, 5943.
5 (a) Pon, R. A.; Lussier, M.; Yang, Q.-L.;
Jennings, H. J. J. Exp. Med.
1997, 185, 1929. (b) Frosch, M.; Gorgen, I;
Boulnois, G. T.; Bitter-
Suermann, D. Proc. Natl. Acad, Sci. U. S. A.
1985, 82, 1194. (c) Liu, T.;
Guo, Z.; Yang, Q.; Sad, S.; Jennings, H. J.
J. Biol. Chem. 2000, 275, 32832.
6 (a) Kuduk, S. D.; Schwarz, J. B.; Chen, X.
T.; Glunz, P. W.; Sames, D.;
Ragupathi, G.; Livingston, P. O.;
Danishefsky, S. J. J. Am. Chem. Soc.
1998, 120, 12474. (b) Schwarz, J. B.; Kuduk,
S. D.; Chen, X. T.; Sames, D.;
Glunz, P. W.; Danishefsky, S. J. J. Am.
Chem. Soc. 1999, 121, 2662.
7 GLYCOBIOLOGY AND MEDICINE John S. Axford. Ed.
Kluwer Academic/Plenum, Inc.
New York, 2003, pp. 163-165.
8 (a) Tuerk, C.; Gold, L. Science 1990, 249
(4968), 505. (b) Ellington, A.
D.; Szostak, J. W. Nature 1990, 346, 818.
9 (a) Yoshihiro, I.; Naok, K.; Yukio, I.
Methods 2000, 22, 107. (b)
Vianini, E. ; Palumbo, M.; Gatto, B. Bioorg.
Med. Chem. 2001, 9, 2543. (c)
Williams, K. P.; Liu, X-H.; Schumacher, T.
N. M.; Lin, H. Y.; Ausiello, D.
A.; Kim, P. S.; Bartel, D. P. Proc. Natl.
Acad. Sci. U. S. A. 1997, 94,
11285.
10 (a) Gold, L. J. Biol. Chem. 1995, 270, 13581.
(b) Drolet, D. W.; Moon-
McDermott, L.; Roming, T. S. Nat.
Biotechnol. 1996, 14, 1021. (c) Conrad,
R.; Ellington, A. D. Anal. Biochem. 1996,
242, 261. (d) Potyrailo, R. A.;
Conrad, R. C.; Ellington, A. D.; Hieftje, G.
M. Anal. Chem. 1998, 70, 3419.
11 Nelson, D. L.; Michael, M. Lehninger
Principles of Biochemistry. Worth,
Inc., New York, 2000, pp. 1129-1148.
12 (a) Rajendran, M.; Ellington, A. D. Optical
Biosensors: Present and
Future. Elsevier Science BV, Amsterdam,
2002, pp. 369-396. (b) Rajendran,
M.; Ellington, A. D. Comb. Chem. High
Throughput Screen 2002, 5, 263.
13 Mhlanga, M. M.; Malmberg, L. Methods 2001,
25, 463.
14 Miyawaki, A.; Llopis, J.; Helm, R.;
McCaffery, J. M.; Adams, J. A.;
Ikura, M.; Tsien, R. Y. Nature 1997, 388,
882.
15 (a) Thompson, R. B.; Maliwal, B. P.;
Feliccia, V. L.; Fierke, C. A.;
McCall, K. Anal. Chem. 1998, 70, 4717. (b)
Walkup, G. K.; Imperiali, B.
J. Am. Chem. Soc. 1996, 118, 3053. (c)
Godwin, H. A.; Berg, J. M. J. Am.
Chem. Soc. 1996, 118, 6514.
16 (a) Hesselberth, J.; Robertson, M. P.;
Jhaveri, S.; Ellington, A. D. Rev.
Mol. Biotechnol. 2000, 74, 15. (b)
Jayasena, S. D. Clin. Chem. 1999, 45,
1628.
17 Wilson, D. S.; Szostak, J. W. Annu. Rev.
Biochem. 1999, 68, 611.
18 (a) Li, J.; Fang, X.; Schuster, S.; Liu, X.;
Tan, W. Angew. Chem. Int. Ed.
Engl. 2000, 39, 1049. (b) Fang, X.; Li, J.
J.; Tan, W. U. Anal. Chem.
2000, 72, 3280.
19 (a) Famulok, M.; Mayer, G.; Blind, M. Acc.
Chem. Res. 2000, 33 (9), 591.
(b) Wilson, D. S.; Szostak, J. W. Annu. Rev.
Biochem. 1999, 68, 611.
20 Drolet, D. W.; Moon-McDermott, L.; Romig, T.
S. Nat. Biotechnol. 1996,
14, 1021.
21 (a) Lee, M.; Walt, D. R. Anal. Biochem.
2000, 282, 142. (b) Rajendran, M.;
Ellington, A. D. Optical Biosensors:
Present and Future In Ligler, F. S.;
Rowe Taitt, C. A. eds, Elsevier Science BV,
Amsterdam, 2002, pp. 369-396.
(c) McCauley, T. G.; Hamaguchi, N.; Stanton,
M. Anal. Biochem. 2003, 319,
244.
22 Yang, Q. ; Goldstein, I. J. ; Mei, H. Y. ;
Engelke, D. R. Proc. Natl.
Acad. Sci. U. S. A. 1998, 95,
5462.
23 Kawakami, J.; Kawase, Y.; Sugimoto, N. Anal.
Chem. Acta 1998, 365, 95.
24 Jeong, S.; Eom, T. Y.; Kim, S. J.; S.-W.
Lee.; Y u, J. Biochem. Biophys.
Res. Commun. 2001, 281, 237.
25 (a) Rajendran, M.; Ellington, A. D. Nucleic
Acid Res. 2003, 31, 5700. (b)
Tyagi, S.; Kramer, F. R. Nat. Biotechnol.
1996, 14, 303. (c) Nutiu, R.;
Li, Y. Nucleic Acids Res. 2002, 30, E94.
(d) Marras, S. A.; Kramer, F.
R.; Tyagi, S. Methods Mol. Biol. 2003, 212,
111.
26 (a) Jhaveri, S.; Kirby, R.; Conrad, R.;
Maglott, E.; Bowser, M.; Kennedy,
R.T.; Glick, G.; Ellington, A. D. J. Am.
Chem. Soc. 2000, 122, 2469-2473.
(b) Jhaveri, S.; Rajendran, M.; Ellington,
A. D. Nat. Biotechnol. 2000,
18, 1293.
27 (a) Tyagi, S.; Kramer, F. R. Nat.
Biotechnol. 1996, 14, 303. (b)
Tyagi, S.; Marras, S. A. E.; Krame, F. R.
Nat. Biotechnol. 2000, 18,
1191.
28 Nutiu, R.; Li, Y. Nucleic Acids. Res. 2002,
30, E94.
29 Nutiu, R.; Li, Y. J. Am. Chem. Soc. 2003,
125, 4772.
30 Cai, J.; Davison, B. E.; Ganellin, C. R.;
Thaisrivongs, S.; Wibley, K. S.
Carbohyd. Res. 1997, 300, 109.
31 (a)Nashed, M. A.; El-Sokkary, R. I.; Rateb,
L. Carbohydr. Res. 1984, 131,
47. (b) Ahn, Y. M.; Gray, G. R. Carbohydr.
Res. 1996, 296, 215.
32 Wang, L.-X.; Lee, Y. C. J. Chem. Soc.
Perkin Trans. 1 1996, 581.
33 Igor, A. K.; Shenlan, M.; Yue, Xu.; Xuefei
Huang.; Lac Lee.; Pamela S.
S.; Changshou. Gao.; Avery R.; Coyle, Kim
D.; Janda.; Chi-Huey Wong.
Chembiochem. 2001, 2, 741.
34 Blix, G. Acta. Chem. Scand. 1948, 2, 467.
35 Ramachandran, A.; Flinchbaugh, J.; Ayoubi,
P.; Olah, G. A.; Malayer, J.
R. Biosensors Bioelectronics 2004, 19, 727.
36 Sambrook, J.; Fritsch, E. F.; Maniatis, T.
Molecular Cloning A Laboratory
Manual/Second Edition Nolan, C. Ed. Clod
Spring Harbor Laboratory, Inc.
United States of America, 1989, pp. E11-E15.
37 (a) Smith, L. M.; Fung, S.; Hunkapiller, M.
W.; Hunkapiller, T. J.; Hood,
L. E. Nucleic Acids Res. 1985, 13, 2399.
(b) Imanishi, Y.; Ito, Y.;
Suzuki, A.; Kawazoe, N. Bioconjug. Chem.
2001, 12, 850.
38 (a) Kool, E. T.; Ohmichi, T.; Maki, A. Proc.
Natl. Acad. Sci. U. S. A.
2002, 99, 54. (b) Uhlen, M.; Wahlberg,
J.;Lunderberg, J.; Hultman, T.
Proc. Natl. Acad. Sci. U. S. A. 1990, 87,
6569. (c) Lundeberg, J.; O’
Meara, D.; Nilsson, P.; Nygren, P.; Uhlen,
M. Anal. Biochem. 1998, 255,
195.
39 (a) Ellington, A. D.; Rajendran, M. Nucleic
Acids Res. 2003, 31, 19. 5700.
(b) Ellington, A. D.; Matthew, L. Bioorg.
Med. Chem. 2001, 9, 2581. (c)
Toole, J. J.; Bock, L. C.; Griffin, L. C.;
Latham, J. A.; Vermaas, E. H.
Nature 1992, 355, 564.
40 Ellington, A. D.; Szostak, J. W. Nature
1992, 355, 850.