Center for BioEnergetics, The Biodesign Institute, and Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
Bioorg Med Chem. 2011 Jun 15;19(12):3831-44. doi: 10.1016/j.bmc.2011.04.047. Epub 2011 Apr 28.
Previous studies have indicated that the methylvalerate subunit of bleomycin (BLM) plays an important role in facilitating DNA cleavage by BLM and deglycoBLM. Eleven methylvalerate analogues have been synthesized and incorporated into deglycoBLM congeners by the use of solid-phase synthesis. The effect of the valerate moiety in the deglycoBLM analogues has been studied by comparison with the parent deglycoBLM A(5) using supercoiled DNA relaxation and sequence-selective DNA cleavage assays. All of the deglycoBLM analogues were found to effect the relaxation of the plasmid DNA. Those analogues having aromatic C4-substituents exhibited cleavage efficiency comparable to that of deglycoBLM A(5). Some, but not all, of the deglycoBLM analogues were also capable of mediating sequence-selective DNA cleavage.
先前的研究表明博来霉素（BLM）的异戊酸甲酯侧链在促进 BLM 和去糖基 BLM 介导的 DNA 切割中起着重要作用。已经合成了 11 种异戊酸甲酯类似物，并通过固相合成将其掺入去糖基 BLM 同系物中。通过与亲本去糖基 BLM A(5)进行超螺旋 DNA 松弛和序列选择性 DNA 切割实验，研究了去糖基 BLM 类似物中异戊酸甲酯部分的作用。所有的去糖基 BLM 类似物都被发现能影响质粒 DNA 的松弛。那些具有芳香族 C4-取代基的类似物表现出与去糖基 BLM A(5)相当的切割效率。一些（但不是全部）去糖基 BLM 类似物也能够介导序列选择性 DNA 切割。
