一对具有DNA切割功能的新型酰胺对映体

高等学校化学学报 ›› 2004, Vol. 25 ›› Issue (6): 1065.

一对具有DNA切割功能的新型酰胺对映体

朱长进^1,3, 路杨², 杜海莲², 蒋宇扬¹, 赵玉芬^1,2

1. 清华大学生命科学与工程研究院, 化学系, 化学生物学与生命有机磷化学教育部重点实验室, 北京 100084;
2. 厦门大学化学系, 厦门 361005;
3. 北京理工大学化工与环境学院, 北京 100081

收稿日期:2003-05-09 出版日期:2004-06-24 发布日期:2004-06-24
通讯作者: 赵玉芬(1948年出生),女,博士,教授,博士生导师,中国科学院院士,主要从事生命有机磷化学研究.E-mail:yfzhao@mail.tsinghua.edu.cn E-mail:yfzhao@mail.tsinghua.edu.cn
基金资助:
国家自然科学重点基金(批准号:20132020);福建省自然科学基金(批准号:2001F008)资助

A Pair of New Enantiomeric Amides with DNA-cleaving Function

ZHU Chang-Jin^1,3, LU Yang², DU Hai-Lian², JIANG Yu-Yang¹, ZHAO Yu-Fen^1,2

1. Bioorganic Phosphorus Chemistry Laboratory of Ministry Education, Department of Chemistry, School of Life Science and Engineering, Tsinghua University, Beijing 100084, China;
2. Department of Chemistry, Xiamen University, Xiamen 361005, China;
3. School of Chemical Engineering and Environment, Beijing Institute of Technology, Beijing 100081, China

Received:2003-05-09 Online:2004-06-24 Published:2004-06-24

摘要/Abstract

摘要： 设计合成一对新型的丝氨酸-组胺酰胺对映体化合物L-Ser-Hism和D-Ser-Hism,发现它们具有明显的DNA切割活性,切割反应的最佳pH范围为6.0～6.5.L-Ser-Hism的切割活性比D-Ser-Hism的强.与丝组二肽相比,这对酰胺对映体未显示出明显的切割蛋白活性,表明其对DNA的优先切割功能.

关键词: 丝氨酸-组胺酰胺, DNA, 切割

Abstract: A number of small molecules have been shown to hydrolyze RNA as probes in RNA structure studies but very few reports have been found that small molecules can hydrolyze DNA. Previously we found that ser-his dipeptide could cut DNA probably via a hydrolytic mechanism,and also showed protein-cleaving activity. We have focused on developing additional small molecules with DNA cleavage activity and studying their mechanism in the cleavage. In the present study,we designed a pair of new enantiomeric serine/histamine amides,L-Ser-Hism and D-Ser-Hism. These two amides were synthesized by coupling of L- and D-serine with histamine,respectively,using the common DCC peptide synthesis method. Their function was assessed by the electrophoresis of DNA products,which were produced from the incubation of the amides with DNA. It was found that both of the amides were capable of cleaving DNA significantly at optimal pH=6.0——6.5,and that the isomer L-Ser-Hism showed a stronger cleavage function than the other isomer D-Ser-Hism. However,they could not cleave the protein BSA when the amides were tested in the protein cleavage experiment. These findings suggest the preferential DNA cleavage function of the amides.

Key words: Serine-histamine amide, DNA, Cleavage

中图分类号:

O61.29

TrendMD:

朱长进, 路杨, 杜海莲, 蒋宇扬, 赵玉芬. 一对具有DNA切割功能的新型酰胺对映体. 高等学校化学学报, 2004, 25(6): 1065.

ZHU Chang-Jin, LU Yang, DU Hai-Lian, JIANG Yu-Yang, ZHAO Yu-Fen. A Pair of New Enantiomeric Amides with DNA-cleaving Function. Chem. J. Chinese Universities, 2004, 25(6): 1065.

参考文献

[1] Sigman D.S.,Maz umder A.,Perrin D.M..Chem.Rev.[J],1993,93:2 295—2 316 [2] Uhlmann E.,Peymen A..Chem.Rev.[J],1990,90:543—584 [3] Gieg R.,Felden B.,Zenkova M.A.et al..Met hods Enzymol.[J],2000,318:147—165 [4] Chandler A.J.,Kirby A.J..J.Chem.Soc.Chem.Commun.[J],1992:1 769—1 700 [5] Helm M.,Kopka M.L.,Sharma S.K.et al..Biochem.Biophys.Res.Commun.[J],2001,281:1 283—1 290 [6] Ehresmann C.,Baudin F.,Mougel M.et al..Nucleic Acids Res.[J],1987,15:9 109—9 128 [7] Krol A.,Carbon P..Met hods Enzymol.[J],1989,180:212—227 [8] Kolch anov N.A.,Titov I.I.,Vlassova I.E.et al..Prog.Nucleic Acid Res.Mol.Bio.[J],1996,53:131—197 [9] Sigman D.S.,Chen C.H.B..An nu.Rev.Biochem.[J],1990,59:207—236 [10] Sigman D.S..Biochemist ry[J],1990,29:9 097—9 105 [11] McPherson A.,Brayer G.,Cascio D.et al..Science[J],1986,232:765—768 [12] Blow D.M..Acc.Ch em.Res.[J],1976,9:145—152 [13] Lambow itz A.M.,Belf ort M..Annu.Rev.Biochem.[J],1993,62:587—622 [14] Xu M.Q.,Sout hw ort h M.W.,Mersha F.B.et al..Cell[J],1993,75:1 371—1 377 [15] Perler F.B..Cell[J],1998,92:1—4 [16] Perler F.B.,Xu M.Q.,Paulus H..Curr.Opin.Chem.Biol.[J],1997,1:292—299 [17] Zhao Y.,Cao P.;Eds.by Chela-Flores J.,Raulin F..Chemical Evolut ion:Physics of t he Origin and Evolut ion of Lif e[M],Net her-lands:Kluw er Academic Publisher,1996:279—285 [18] Li X.,Zhao Y..Chinese Chem.Let t.[J],1997,8:611—612 [19] Li Y.,Yin Y.,Zhao Y..Int.J.Pept ide Prot ein Res.[J],1992,39:375—381 [20] Zhao Y.,Ju Y.,Li Y.et al..Int.J.Pept ide Prot ein Res.[J],1995,45:1—5 [21] Ju Y.,Zh ao Y.,Sha Y.et al..Phosphorus,Sulf ur,Silicon and Relat ed Elem ent s[J],1995,101:117—123 [22] Li Y.,Zhao Y.,Hat field S.et al..Bioorg.Med.Chem.[J],2000,8:2 675—2 680 [23] WAN Rong(万　荣),W A N G Ning(王　宁),ZHAO Gang(赵　刚)et al..Ch em.J.Chinese Universities(高等学校化学学报) [J],2000,21(12):1 864—1 866 [24] Li Y.,Hat field S.,Li J.et al..Bioorg.Med.Chem.[J],2002,10:667—673 [25] WAN Rong(万　荣),WANG Ning(王　宁),ZHAO Yu-Fen(赵玉芬).Chem.J.Chinese Universities(高等学校化学学报)[J],2001,22(4):598—600 [26] Chen J.,Wan R.,Liu H.et al..Let t.Pept ide Sci.[J],2001,7:325—329