X-RAY-ANALYSIS OF 2',3'-LYXOANHYDROTHYMIDINE, A CONFORMATIONALLY RESTRICTED INHIBITOR OF RETROVIRAL REVERSE TRANSCRIPTASES

被引:20
作者
GURSKAYA, GV [1 ]
BOCHKAREV, AV [1 ]
ZDANOV, AS [1 ]
PAPCHIKHIN, AV [1 ]
PURYGIN, PP [1 ]
KRAYEVSKY, AA [1 ]
机构
[1] KUYBYSHEV STATE UNIV,KUYBYSHEV 443086,USSR
关键词
2'; 3'-Lyxoanhydrothymidine; DNA biosynthesis; Reverse transcriptase; X-ray analysis;
D O I
10.1016/0014-5793(90)80884-L
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
2',3'-Lyxoanhydrothymidine (LAT), a conformationally restricted inhibitor of retroviral reverse transcriptases, has been studied by X-ray analysis. The unit cell contains two crystallographically independent molecules A and B. Their sugar moieties have an identical structure: an 04'-endo pucker of the furanose cycle and a trans conformation about the exocyclic C4'-C5' bond. The conformations of A and B molecules differ with respect to the N-glycosidic bond: χA(04 'Cl' N1C2) = -121.9° which is typical of a common anti conformation whereas χB (04'Cl'N1C2) = 121.2° corresponds to a rare high-syn conformation. All the conformation properties of LAT molecules stem from the presence of an epoxide cycle in their molecules. © 1990.
引用
收藏
页码:63 / 66
页数:4
相关论文
共 15 条
[1]   CONFORMATIONAL-ANALYSIS OF SUGAR RING IN NUCLEOSIDES AND NUCLEOTIDES - NEW DESCRIPTION USING CONCEPT OF PSEUDOROTATION [J].
ALTONA, C ;
SUNDARALINGAM, M .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1972, 94 (23) :8205-+
[2]   AZIDOTHYMIDINE - CRYSTAL-STRUCTURE AND POSSIBLE FUNCTIONAL-ROLE OF THE AZIDO GROUP [J].
CAMERMAN, A ;
MASTROPAOLO, D ;
CAMERMAN, N .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (23) :8239-8242
[3]   INACTIVATION OF DNA-POLYMERASE-I (KLENOW FRAGMENT) BY ADENOSINE 2',3'-EPOXIDE 5'-TRIPHOSPHATE - EVIDENCE FOR THE FORMATION OF A TIGHT-BINDING INHIBITOR [J].
CATALANO, CE ;
BENKOVIC, SJ .
BIOCHEMISTRY, 1989, 28 (10) :4374-4382
[4]   NUCLEOSIDE 5'-TRIPHOSPHATES WITH MODIFIED SUGARS AS SUBSTRATES FOR DNA-POLYMERASES [J].
CHIDGEAVADZE, ZG ;
BEABEALASHVILLI, RS ;
KRAYEVSKY, AA ;
KUKHANOVA, MK .
BIOCHIMICA ET BIOPHYSICA ACTA, 1986, 868 (2-3) :145-152
[5]  
Chidzhavadze Z G, 1989, Mol Biol (Mosk), V23, P1732
[6]   PROPERTIES OF 2',3'-DIDEOXY-2',3'-DEHYDROTHYMIDINE 5'-TRIPHOSPHATE IN TERMINATING DNA-SYNTHESIS CATALYZED BY SEVERAL DIFFERENT DNA-POLYMERASES [J].
DYATKINA, N ;
MINASSIAN, S ;
KUKHANOVA, M ;
KRAYEVSKY, A ;
VONJANTALIPINSKY, M ;
CHIDGEAVADZE, Z ;
BEABEALASHVILLI, R .
FEBS LETTERS, 1987, 219 (01) :151-155
[7]   NMR-STUDIES OF CONFORMATIONS AND INTERACTIONS OF SUBSTRATES AND RIBONUCLEOTIDE TEMPLATES BOUND TO THE LARGE FRAGMENT OF DNA-POLYMERASE-I [J].
FERRIN, LJ ;
MILDVAN, AS .
BIOCHEMISTRY, 1986, 25 (18) :5131-5145
[8]  
FRENZ BA, 1985, ENRAFNONIUS SDP PLUS
[9]  
GURSKAIA GV, 1986, DOKL AKAD NAUK SSSR+, V291, P854
[10]   CRYSTAL-STRUCTURE AND ANTI HERPES-SIMPLEX VIRUS ACTIVITY OF 2,2'-ANHYDRO-1-BETA-D-ARABINOFURANOSYLTHYMINE [J].
HARRISON, DH ;
SCHINAZI, RF ;
RUBIN, BH .
JOURNAL OF MEDICINAL CHEMISTRY, 1982, 25 (12) :1507-1510