Deglycobleomycin A6 analogues modified in the methylvalerate moiety

Xiaoqing Cai; Paul A. Zaleski; Ali Cagir; Sidney Hecht

doi:10.1016/j.bmc.2011.04.047

Deglycobleomycin A₆ analogues modified in the methylvalerate moiety

Xiaoqing Cai, Paul A. Zaleski, Ali Cagir, Sidney Hecht

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

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 A₅ 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 A₅. Some, but not all, of the deglycoBLM analogues were also capable of mediating sequence-selective DNA cleavage.

Original language	English (US)
Pages (from-to)	3831-3844
Number of pages	14
Journal	Bioorganic and Medicinal Chemistry
Volume	19
Issue number	12
DOIs	https://doi.org/10.1016/j.bmc.2011.04.047
State	Published - Jun 15 2011

Keywords

Bleomycins
DNA cleavage
Deglycobleomycin analogues
Methylvalerate moiety
Solid-phase synthesis

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmc.2011.04.047

Cite this

@article{b0aebff2d6f3477fb3000d26801b02f9,

title = "Deglycobleomycin A6 analogues modified in the methylvalerate moiety",

abstract = "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 A5 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 A5. Some, but not all, of the deglycoBLM analogues were also capable of mediating sequence-selective DNA cleavage.",

keywords = "Bleomycins, DNA cleavage, Deglycobleomycin analogues, Methylvalerate moiety, Solid-phase synthesis",

author = "Xiaoqing Cai and Zaleski, {Paul A.} and Ali Cagir and Sidney Hecht",

year = "2011",

month = jun,

day = "15",

doi = "10.1016/j.bmc.2011.04.047",

language = "English (US)",

volume = "19",

pages = "3831--3844",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Limited",

number = "12",

}

TY - JOUR

T1 - Deglycobleomycin A6 analogues modified in the methylvalerate moiety

AU - Cai, Xiaoqing

AU - Zaleski, Paul A.

AU - Cagir, Ali

AU - Hecht, Sidney

PY - 2011/6/15

Y1 - 2011/6/15

N2 - 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 A5 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 A5. Some, but not all, of the deglycoBLM analogues were also capable of mediating sequence-selective DNA cleavage.

AB - 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 A5 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 A5. Some, but not all, of the deglycoBLM analogues were also capable of mediating sequence-selective DNA cleavage.

KW - Bleomycins

KW - DNA cleavage

KW - Deglycobleomycin analogues

KW - Methylvalerate moiety

KW - Solid-phase synthesis

UR - http://www.scopus.com/inward/record.url?scp=79958282322&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79958282322&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2011.04.047

DO - 10.1016/j.bmc.2011.04.047

M3 - Article

C2 - 21612932

AN - SCOPUS:79958282322

SN - 0968-0896

VL - 19

SP - 3831

EP - 3844

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 12

ER -