STEREOELECTRONIC PROPERTIES OF 5 ANTI-HSV-1 2'DEOXYNUCLEOSIDES ANALOGS WITH HETEROCYCLIC SUBSTITUENTS IN THE 5-POSITION - A COMPARISON WITH BVDU

被引：11

作者：

OLIVIER, A ^{[1
]}

CREUVEN, I ^{[1
]}

EVRARD, C ^{[1
]}

EVRARD, G ^{[1
]}

DORY, M ^{[1
]}

VANAERSCHOT, A ^{[1
]}

WIGERINCK, P ^{[1
]}

HERDEWIJN, P ^{[1
]}

DURANT, F ^{[1
]}

机构：

[1] CATHOLIC UNIV LEUVEN,REGA INST MED RES,MED CHEM LAB,B-3000 LOUVAIN,BELGIUM

来源：

ANTIVIRAL RESEARCH | 1994年 / 24卷 / 04期

关键词：

ANTIVIRAL ACTIVITY; HERPES SIMPLEX VIRUS TYPE 1; 5-(2-BROMOVINYL)-2'-DEOXYURIDINE ANALOG; SINGLE CRYSTAL X-RAY DIFFRACTION; MO CALCULATION;

D O I：

10.1016/0166-3542(94)90076-0

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Structural and electronic characteristics of 5-(5-chlorothien-2-yl)-2'-deoxyuridine (I), 5-(furan-2-yl)-2'-deoxyuridine (II), 5-(5-bromofuran-2-yl)-2'-deoxyuridine (III), 5-(3-bromoisoxazol-5-yl)-2'-deoxyuridine (V) and 5-(isoxazol-5-yl)-2'-deoxyuridine (IV) have been determined and compared to the BVDU (VI) characteristics in order to explain their respective affinity for the herpes simplex virus type 1 thymidine kinase (TK). Molecular structure of 5-(5-chlorothien-2-yl)-2'-deoxyuridine has been obtained using single crystal X-ray crystallography. Electrostatic potential maps, energy and topology of frontier orbitals were computed at the ab initio MO STO-3G and STO-3G level. These studies reveal that the electrostatic potential energy maps are clearly dependent on the affinity of the compound for the enzyme.

引用

页码：289 / 304

页数：16

共 26 条

[1] BONDING BETWEEN NONBONDED SULFUR AND OXYGEN-ATOMS IN SELECTED ORGANIC-MOLECULES (A QUANTUM CHEMICAL STUDY) [J].

ANGYAN, JG ;

POIRIER, RA ;

KUCSMAN, A ;

CSIZMADIA, IG .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1987, 109 (08) :2237-2245

[2]

BAUDOUX G, 1989, CPS CONTOURING PLOTT

[3]

BOHMAN C, 1993, 4TH S EUR SOC STUD P

[4] HUMAN THYMIDINE KINASE GENE - MOLECULAR-CLONING AND NUCLEOTIDE-SEQUENCE OF A CDNA EXPRESSIBLE IN MAMMALIAN-CELLS [J].

BRADSHAW, HD ;

DEININGER, PL .

MOLECULAR AND CELLULAR BIOLOGY, 1984, 4 (11) :2316-2320

[5]

COEN DM, 1991, ANTIVIR RES, V15, P187

[6] SELF-CONSISTENT MOLECULAR-ORBITAL METHODS .17. GEOMETRIES AND BINDING-ENERGIES OF 2ND-ROW MOLECULES - COMPARISON OF 3 BASIS SETS [J].

COLLINS, JB ;

SCHLEYER, PV ;

BINKLEY, JS ;

POPLE, JA .

JOURNAL OF CHEMICAL PHYSICS, 1976, 64 (12) :5142-5151

[7] CONSTRUCTION AND CHARACTERIZATION OF A RECOMBINANT PLASMID ENCODING THE GENE FOR THE THYMIDINE KINASE OF HERPES-SIMPLEX TYPE-1 VIRUS [J].

ENQUIST, LW ;

VANDEWOUDE, GF ;

WAGNER, M ;

SMILEY, JR ;

SUMMERS, WC .

GENE, 1979, 7 (3-4) :335-342

[8] SEQUENCE, STRUCTURE AND PROMOTER CHARACTERIZATION OF THE HUMAN THYMIDINE KINASE GENE [J].

FLEMINGTON, E ;

BRADSHAW, HD ;

TRAINADORGE, V ;

SLAGEL, V ;

DEININGER, PL .

GENE, 1987, 52 (2-3) :267-277

[9]

FOLKERS G, 1991, J COMP AIDED MOL DES, V5, P387

[10] SELF-CONSISTENT MOLECULAR-ORBITAL METHODS .I. USE OF GAUSSIAN EXPANSIONS OF SLATER-TYPE ATOMIC ORBITALS [J].

HEHRE, WJ ;

STEWART, RF ;

POPLE, JA .

JOURNAL OF CHEMICAL PHYSICS, 1969, 51 (06) :2657-+

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