Synthesis of a pentasaccharide-oligonucleotide conjugate: A novel antithrombotic agent

被引：8

作者：

Buijsman, RC

Kuijpers, WHA

Basten, JEM

KuylYeheskiely, E

vanderMarel, GA

vanBoeckel, CAA

vanBoom, JH

机构：

[1] LEIDEN UNIV,LEIDEN INST CHEM,GORLAEUS LABS,NL-2300 RA LEIDEN,NETHERLANDS

[2] NV ORGANON,DEPT MED CHEM,NL-5340 BH OSS,NETHERLANDS

来源：

CHEMISTRY-A EUROPEAN JOURNAL | 1996年 / 2卷 / 12期

关键词：

antithrombotics; enzyme inhibitors; oligonucleotides; oligosaccharides; protecting groups;

D O I：

10.1002/chem.19960021216

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Derivatization of the octadecathymidylate derivative 18 (T-18 ODN) containing a free amine function with sulfo-SIAB(R) gave the corresponding iodoacetyl ODN 21. Conjugation of the latter with the thiol-containing pentasaccharide 17c gave pentasaccharide-ODN conjugate III, which exhibited anti-Xa and antithrombin activities of 173 U mg(-1) and 5 U mg(-1), respectively.

引用

收藏

页码：1572 / 1577

页数：6

相关论文

共 28 条

[1] STRUCTURE-ACTIVITY RELATIONSHIP IN HEPARIN - A SYNTHETIC PENTASACCHARIDE WITH HIGH-AFFINITY FOR ANTI-THROMBIN-III AND ELICITING HIGH ANTI-FACTOR-XA ACTIVITY [J].

CHOAY, J ;

PETITOU, M ;

LORMEAU, JC ;

SINAY, P ;

CASU, B ;

GATTI, G .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1983, 116 (02) :492-499

[2] CHEMICAL SYNTHESIS OF OLIGONUCLEOTIDES CONTAINING A FREE SULFHYDRYL-GROUP AND SUBSEQUENT ATTACHMENT OF THIOL SPECIFIC PROBES [J].

CONNOLLY, BA ;

RIDER, P .

NUCLEIC ACIDS RESEARCH, 1985, 13 (12) :4485-4502

[3]

DANIELSSON A, 1986, J BIOL CHEM, V261, P5467

[4] SELECTIVE CLEAVAGE OF ANOMERIC ACETYL GROUPS OF ACETYLATED GLYCOSYL RESIDUES BY HYDRAZINE [J].

EXCOFFIER, G ;

GAGNAIRE, D ;

UTILLE, JP .

CARBOHYDRATE RESEARCH, 1975, 39 (02) :368-373

[5] A NOVEL, REDUCTIVE RING-OPENING OF CARBOHYDRATE BENZYLIDENE ACETALS, WITH UNUSUAL REGIOSELECTIVITY [J].

GAREGG, PJ ;

HULTBERG, H .

CARBOHYDRATE RESEARCH, 1981, 93 (01) :C10-C11

[6] RATIONAL DESIGN OF SYNTHETIC HEPARIN ANALOGS WITH TAILOR-MADE COAGULATION-FACTOR INHIBITORY ACTIVITY [J].

GROOTENHUIS, PDJ ;

WESTERDUIN, P ;

MEULEMAN, D ;

PETITOU, M ;

VANBOECKEL, CAA .

NATURE STRUCTURAL BIOLOGY, 1995, 2 (09) :736-739

[7] SPECIFIC RECOGNITION OF ANTIBODY OLIGONUCLEOTIDE CONJUGATES BY RADIOLABELED ANTISENSE NUCLEOTIDES - A NOVEL-APPROACH FOR 2-STEP RADIOIMMUNOTHERAPY OF CANCER [J].

KUIJPERS, WHA ;

BOS, ES ;

KASPERSEN, FM ;

VEENEMAN, GH ;

VANBOECKEL, CAA .

BIOCONJUGATE CHEMISTRY, 1993, 4 (01) :94-102

[8]

Lane D. A., 1989, HEPARIN CHEM BIOL PR

[9] ANTICOAGULANT ACTIVITIES OF HEPARIN OLIGOSACCHARIDES AND THEIR NEUTRALIZATION BY PLATELET FACTOR-4 [J].

LANE, DA ;

DENTON, J ;

FLYNN, AM ;

THUNBERG, L ;

LINDAHL, U .

BIOCHEMICAL JOURNAL, 1984, 218 (03) :725-732

[10] ASSAY OF PLASMA HEPARIN USING THROMBIN AND CHROMOGENIC SUBSTRATE H-D-PHE-PIP-ARG-PNA (S-2238) [J].

LARSEN, ML ;

ABILDGAARD, U ;

TEIEN, AN ;

GJESDAL, K .

THROMBOSIS RESEARCH, 1978, 13 (02) :285-288