AFFINITY OF THE ANTIVIRAL ENANTIOMERS OF OXATHIOLANE CYTOSINE NUCLEOSIDES FOR HUMAN 2'-DEOXYCYTIDINE KINASE

被引：72

作者：

SHEWACH, DS

LIOTTA, DC

SCHINAZI, RF

机构：

[1] VET AFFAIRS MED CTR,1670 CLAIRMONT RD,DECATUR,GA 30033

[2] UNIV MICHIGAN,DEPT PHARMACOL,ANN ARBOR,MI 48109

[3] EMORY UNIV,DEPT CHEM,BIOCHEM PHARMACOL LAB,ATLANTA,GA 30322

[4] EMORY UNIV,DEPT PEDIAT,BIOCHEM PHARMACOL LAB,ATLANTA,GA 30322

来源：

BIOCHEMICAL PHARMACOLOGY | 1993年 / 45卷 / 07期

关键词：

D O I：

10.1016/0006-2952(93)90058-5

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The two enantiomers of 2',3'-dideoxy-3'-thiacytidine (BCH-189) and their 5-fluoro analogs (FTC) were found to be good substrates for human 2'-deoxycytidine kinase with K(m) values in the 5.7 to 42.1 muM range. The affinity of the (-)-enantiomers was greater than that of the (+)-compounds. These results may explain the greater in vitro antiviral potency against human immunodeficiency virus and hepatitis B virus of the (-)-enantiomers when compared to their (+)-counterparts. The (+)- and (-)-enantiomers of FTC and BCH-189 are the first nucleoside analogs for which we have observed lower apparent kinetic constants for this enzyme in the presence of ATP compared to UTP.

引用

收藏

页码：1540 / 1543

页数：4

相关论文

共 19 条

[11] ENZYME-MEDIATED ENANTIOSELECTIVE PREPARATION OF PURE ENANTIOMERS OF THE ANTIVIRAL AGENT 2',3'-DIDEOXY-5-FLUORO-3'-THIACYTIDINE (FTC) AND RELATED-COMPOUNDS [J].

HOONG, LK ;

STRANGE, LE ;

LIOTTA, DC ;

KOSZALKA, GW ;

BURNS, CL ;

SCHINAZI, RF .

JOURNAL OF ORGANIC CHEMISTRY, 1992, 57 (21) :5563-5565

[12] 2',3'-DIDEOXYNUCLEOSIDE PHOSPHORYLATION BY DEOXYCYTIDINE KINASE FROM NORMAL HUMAN THYMUS EXTRACTS - ACTIVATION OF POTENTIAL-DRUGS FOR AIDS THERAPY [J].

JOHNSON, MA ;

JOHNS, DG ;

FRIDLAND, A .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1987, 148 (03) :1252-1258

[13]

KRENITSKY TA, 1976, J BIOL CHEM, V251, P4055

[14] SELECTIVE-INHIBITION OF HUMAN IMMUNODEFICIENCY VIRUSES BY RACEMATES AND ENANTIOMERS OF CIS-5-FLUORO-1-[2-(HYDROXYMETHYL)-1,3-OXATHIOLAN-5-YL]CYTOSINE [J].

SCHINAZI, RF ;

MCMILLAN, A ;

CANNON, D ;

MATHIS, R ;

LLOYD, RM ;

PECK, A ;

SOMMADOSSI, JP ;

STCLAIR, M ;

WILSON, J ;

FURMAN, PA ;

PAINTER, G ;

CHOI, WB ;

LIOTTA, DC .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1992, 36 (11) :2423-2431

[15] ACTIVITIES OF THE 4 OPTICAL ISOMERS OF 2',3'-DIDEOXY-3'-THIACYTIDINE (BCH-189) AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN HUMAN-LYMPHOCYTES [J].

SCHINAZI, RF ;

CHU, CK ;

PECK, A ;

MCMILLAN, A ;

MATHIS, R ;

CANNON, D ;

JEONG, LS ;

BEACH, JW ;

CHOI, WB ;

YEOLA, S ;

LIOTTA, DC .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1992, 36 (03) :672-676

[16]

SCHINAZI RF, 1992, AIDS RES HUM RETROV, V8, P553

[17]

SHEWACH DS, 1992, MOL PHARMACOL, V42, P518

[18] COMPARISON OF CYTOTOXICITY OF THE (-)-ENANTIOMER AND (+)-ENANTIOMER OF 2',3'-DIDEOXY-3'-THIACYTIDINE IN NORMAL HUMAN BONE-MARROW PROGENITOR CELLS [J].

SOMMADOSSI, JP ;

SCHINAZI, RF ;

CHU, CK ;

XIE, MY .

BIOCHEMICAL PHARMACOLOGY, 1992, 44 (10) :1921-1925

[19] ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ACTIVITY AND INVITRO TOXICITY OF 2'-DEOXY-3'-THIACYTIDINE (BCH-189), A NOVEL HETEROCYCLIC NUCLEOSIDE ANALOG [J].

SOUDEYNS, H ;

YAO, XJ ;

GAO, Q ;

BELLEAU, B ;

KRAUS, JL ;

NGHE, NB ;

SPIRA, B ;

WAINBERG, MA .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1991, 35 (07) :1386-1390