The DNA phosphate backbone is not involved in catalysis of the duocarmycin and CC-1065 DNA alkylation reaction

被引：21

作者：

Ambroise, Y

Boger, DL

机构：

[1] Scripps Res Inst, Res Inst, Dept Chem, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 03期

关键词：

D O I：

10.1016/S0960-894X(01)00740-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The rates of DNA alkylation were established for the reaction of (+)-duocarmycin SA (1) with the native duplex d(G(1)TCAATTAGTC(11)).d(G(12)ACTAATTGAC(22)), an 11 bp deoxyoligonucleotide that contains a single high-affinity alkylation site that has been structurally characterized at exquisite resolution, and modified duplexes in which the four backbone phosphates proximal to the C4 carbonyl of bound 1 were replaced with methylphosphonates. All were found to react at comparable rates establishing that these backbone phosphates do not participate in catalysis of the DNA alkylation reaction. (C) 2002 Elsevier Science Ltd. All rights reserved.

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页码：303 / 306

页数：4

相关论文

共 47 条

[1]

Boger D L, 1994, Bioorg Med Chem, V2, P115, DOI 10.1016/S0968-0896(00)82007-6

[2]

Boger D. L., 1991, CHEMTRACTS ORG CHEM, V4, P329

[3] CC-1065 PARTIAL STRUCTURES - ENHANCEMENT OF NONCOVALENT AFFINITY FOR DNA MINOR GROOVE BINDING THROUGH INTRODUCTION OF STABILIZING ELECTROSTATIC INTERACTIONS [J].

BOGER, DL ;

SAKYA, SM .

JOURNAL OF ORGANIC CHEMISTRY, 1992, 57 (04) :1277-1284

[4] DNA ALKYLATION PROPERTIES OF CC-1065 AND DUOCARMYCIN ANALOGS INCORPORATING THE 2,3,10,10A-TETRAHYDROCYCLOPROPA[D]BENZO[F]QUINOL-5-ONE ALKYLATION SUBUNIT - IDENTIFICATION OF SUBTLE STRUCTURAL FEATURES THAT CONTRIBUTE TO THE REGIOSELECTIVITY OF THE ADENINE N3 ALKYLATION REACTION [J].

BOGER, DL ;

MESINI, P .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1995, 117 (47) :11647-11655

[5] A novel class of CC-1065 and duocarmycin analogues subject to mitomycin-related reductive activation [J].

Boger, DL ;

Garbaccio, RM .

JOURNAL OF ORGANIC CHEMISTRY, 1999, 64 (22) :8350-8362

[6] DEMONSTRATION OF A PRONOUNCED EFFECT OF NONCOVALENT BINDING SELECTIVITY ON THE (+)-CC-1065 DNA ALKYLATION AND IDENTIFICATION OF THE PHARMACOPHORE OF THE ALKYLATION SUBUNIT [J].

BOGER, DL ;

ZARRINMAYEH, H ;

MUNK, SA ;

KITOS, PA ;

SUNTORNWAT, O .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (04) :1431-1435

[7] A DEMONSTRATION OF THE INTRINSIC IMPORTANCE OF STABILIZING HYDROPHOBIC BINDING AND NONCOVALENT VANDERWAALS CONTACTS DOMINANT IN THE NONCOVALENT CC-1065/B-DNA BINDING [J].

BOGER, DL ;

INVERGO, BJ ;

COLEMAN, RS ;

ZARRINMAYEH, H ;

KITOS, PA ;

THOMPSON, SC ;

LEONG, T ;

MCLAUGHLIN, LW .

CHEMICO-BIOLOGICAL INTERACTIONS, 1990, 73 (01) :29-52

[8] SECOND DEFINITIVE TEST OF PROPOSED MODELS FOR THE ORIGIN OF THE CC-1065 AND DUOCARMYCIN DNA ALKYLATION SELECTIVITY [J].

BOGER, DL ;

JOHNSON, DS .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1995, 117 (04) :1443-1444

[9] (+)-CC-1065 DNA ALKYLATION - KEY STUDIES DEMONSTRATING A NONCOVALENT BINDING SELECTIVITY CONTRIBUTION TO THE ALKYLATION SELECTIVITY [J].

BOGER, DL ;

MUNK, SA ;

ZARRINMAYEH, H .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1991, 113 (10) :3980-3983

[10] CC-1065 and the duocarmycins: Synthetic studies [J].

Boger, DL ;

Boyce, CW ;

Garbaccio, RM ;

Goldberg, JA .

CHEMICAL REVIEWS, 1997, 97 (03) :787-828

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