Conformationally restricted nucleosides. The reaction of adenosine deaminase with substrates built on a bicyclo[3.1.0]hexane template

被引：32

作者：

Marquez, VE ^{[1
]}

Russ, P

Alonso, R

Siddiqui, MA

Shin, KJ

George, C

Nicklaus, MC

Dai, F

Ford, H

机构：

[1] NCI, Div Basic Sci, Med Chem Lab, NIH, Bethesda, MD 20892 USA

[2] USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA

来源：

NUCLEOSIDES & NUCLEOTIDES | 1999年 / 18卷 / 4-5期

关键词：

D O I：

10.1080/15257779908041487

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：

Adenosine deaminase (ADA) can discriminate between two distinct (North and South), conformationally rigid substrate conformers. (N)-methanocarba-2'dA (4) is deaminated 100 times faster than the antipodal (S)-methanocarba-2'dA (5), whereas a non-rigid analogue, aristeromycin (6), is deaminated at an intermediate rate. These results are in agreement with crystallographic data from ADA-ribonucleoside complexes showing the furanose ring of the bound purine in a C3'-endo (North) conformation. The data presented here suggests that 4 and 5 are useful probes to ascertain conformational preferences by purine metabolizing enzymes.

引用

页码：521 / 530

页数：10

共 16 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] Calculation of relative hydration free energy differences for heteroaromatic compounds: Use in the design of adenosine deaminase and cytidine deaminase inhibitors [J].

Erion, MD ;

Reddy, MR .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1998, 120 (14) :3295-3304

[3] Conformationally locked carbocyclic nucleosides built on a bicyclo[3.1.0]hexane template with a fixed Southern conformation. Synthesis and antiviral activity [J].

Ezzitouni, A ;

Marquez, VE .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1997, (07) :1073-1078

[4] TRANSITION-STATE STABILIZATION BY ADENOSINE-DEAMINASE - 1,6-ADDITION OF WATER TO PURINE RIBONUCLEOSIDE, THE ENZYMES AFFINITY FOR 6-HYDROXY-1,6-DIHYDROPURINE RIBONUCLEOSIDE, AND THE EFFECTIVE CONCENTRATION OF SUBSTRATE WATER AT THE ACTIVE-SITE [J].

JONES, W ;

KURZ, LC ;

WOLFENDEN, R .

BIOCHEMISTRY, 1989, 28 (03) :1242-1247

[5] SYNTHESIS AND BIOLOGICAL STUDY OF THE CYCLOPENTENYL CARBOCYCLIC NUCLEOSIDE ANALOG OF 5-AZACYTIDINE [J].

LIM, BB ;

MARQUEZ, VE ;

DOBYNS, KA ;

COONEY, DA ;

DECLERCQ, E .

NUCLEOSIDES & NUCLEOTIDES, 1992, 11 (06) :1123-1135

[6]

MARQUEZ V, UNPUB

[7] HIV-1 reverse transcriptase can discriminate between two conformationally locked carbocyclic AZT triphosphate analogues [J].

Marquez, VE ;

Ezzitouni, A ;

Russ, P ;

Siddiqui, MA ;

Ford, H ;

Feldman, RJ ;

Mitsuya, H ;

George, C ;

Barchi, JJ .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1998, 120 (12) :2780-2789

[8] Nucleosides with a twist. Can fixed forms of sugar ring pucker influence biological activity in nucleosides and oligonucleotides? [J].

Marquez, VE ;

Siddiqui, MA ;

Ezzitouni, A ;

Russ, P ;

Wang, JY ;

Wagner, RW ;

Matteucci, MD .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (19) :3739-3747

[9] CONFORMATIONAL-CHANGES OF SMALL MOLECULES BINDING TO PROTEINS [J].

NICKLAUS, MC ;

WANG, SM ;

DRISCOLL, JS ;

MILNE, GWA .

BIOORGANIC & MEDICINAL CHEMISTRY, 1995, 3 (04) :411-428

[10] How do the energetics of the stereoelectronic gauche and anomeric effects modulate the conformation of nucleos(t)ides? [J].

Plavec, J ;

Thibaudeau, C ;

Chattopadhyaya, J .

PURE AND APPLIED CHEMISTRY, 1996, 68 (11) :2137-2144

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