Bleomycins: new methods will allow reinvestigation of old issues

被引：53

作者：

Chen, JY

Stubbe, JA ^{[1
]}

机构：

[1] MIT, Dept Chem, Cambridge, MA 02139 USA

[2] MIT, Dept Biol, Cambridge, MA 02139 USA

来源：

CURRENT OPINION IN CHEMICAL BIOLOGY | 2004年 / 8卷 / 02期

关键词：

D O I：

10.1016/j.cbpa.2004.02.008

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：

The bleomycins (BLMs) are used clinically in combination chemotherapy, their clinical usefulness being limited by the accompanying pulmonary toxicity. Much has been learned about the structure and function of BLMs in vitro. However, the mechanism of their cytoxicity in vivo, including their target(s), metal cofactor(s) effecting nucleic acid cleavage and its (their) oxidation state, concentrations of BLM in the nucleus of the cell, BLM metabolism, hot spots for double-strand DNA cleavage, and their repair, have remained elusive. New methods offer new opportunities to revisit and solve old problems, which could ultimately lead to development of a more effective therapeutic.

引用

收藏

页码：175 / 181

页数：7

相关论文

共 40 条

[1] RNA cleavage and inhibition of protein synthesis by bleomycin [J].

Abraham, AT ;

Lin, JJ ;

Newton, DL ;

Rybak, S ;

Hecht, SM .

CHEMISTRY & BIOLOGY, 2003, 10 (01) :45-52

[2] Metallobleomycin-mediated cleavage of DNA not involving a threading-intercalation mechanism [J].

Abraham, AT ;

Zhou, X ;

Hecht, SM .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2001, 123 (22) :5167-5175

[3] SEQUENCE-SPECIFIC DOUBLE-STRAND CLEAVAGE OF DNA BY FE BLEOMYCIN .2. MECHANISM AND DYNAMICS [J].

ABSALON, MJ ;

WU, W ;

KOZARICH, JW ;

STUBBE, J .

BIOCHEMISTRY, 1995, 34 (06) :2076-2086

[4] Expanding pyrimidine diphosphosugar libraries via structure-based nucleotidylyltransferase engineering [J].

Barton, WA ;

Biggins, JB ;

Jiang, JQ ;

Thorson, JS ;

Nikolov, DB .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (21) :13397-13402

[5] Structure, mechanism and engineering of a nucleotidylyltransferase as a first step toward glycorandomization [J].

Barton, WA ;

Lesniak, J ;

Biggins, JB ;

Jeffrey, PD ;

Jiang, JQ ;

Rajashankar, KR ;

Thorson, JS ;

Nikolov, DB .

NATURE STRUCTURAL BIOLOGY, 2001, 8 (06) :545-551

[6] Definition of the effect and role of the bleomycin A2 valerate substituents:: Preorganization of a rigid, compact conformation implicated in sequence-selective DNA cleavage [J].

Boger, DL ;

Ramsey, TM ;

Cai, H ;

Hoehn, ST ;

Stubbe, J .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1998, 120 (36) :9149-9158

[7] A systematic evaluation of the bleomycin A2 L-threonine side chain:: Its role in preorganization of a compact conformation implicated in sequence-selective DNA cleavage [J].

Boger, DL ;

Ramsey, TM ;

Cai, H ;

Hoehn, ST ;

Stubbe, JA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1998, 120 (36) :9139-9148

[8]

Boger DL, 1999, ANGEW CHEM INT EDIT, V38, P448, DOI 10.1002/(SICI)1521-3773(19990215)38:4<448::AID-ANIE448>3.0.CO

[9]

2-W

[10] Cleavage of nucleic acids by bleomycin [J].

Burger, RM .

CHEMICAL REVIEWS, 1998, 98 (03) :1153-1169

← 1 2 3 4 →