N-methyl threonine analogues of deglycobleomycin A(2): Synthesis and evaluation

被引：15

作者：

Boger, DL

Teramoto, S

Cai, H

机构：

[1] Department of Chemistry, Scripps Research Institute, 10550 North Torrey Pines Road, San Diego

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 1997年 / 5卷 / 08期

关键词：

D O I：

10.1016/S0968-0896(97)00107-7

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 synthesis of 5 and its D-allo-threonine epimer 6 and the comparison of their DNA cleavage efficiency and selectivity with that of deglycobleomycin A(2) (3) are detailed. The studies illustrate that N-methylation of the L-threonine subunit within deglycobleomycin A(2) dramatically reduces the DNA cleavage efficiency (10-15-fold), weakens and nearly abolishes the inherent DNA cleavage selectivity, but has little effect on the inherent oxidation capabilities of the activated Fe(III) complexes. The results are consistent with a previously unrecognized prominent role for the threonine NH and the potential importance of a hydrogen bond to the Fe(III) hydroperoxide complex of bleomycin or a subsequent activated complex implicated in recent structural models. (C) 1997 Elsevier Science Ltd.

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页码：1577 / 1589

页数：13

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