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Minor-groove Binders (minor-groove + binder)

Distribution by Scientific Domains
Chemistry100%

Selected Abstracts

Extended Target Sequence Specificity of PNA,Minor-Groove Binder Conjugates

CHEMBIOCHEM, Issue 1 2005
Peter E. Nielsen Prof.
,Conjugal bliss. We show that a peptide nucleic acid,Hoechst conjugate (see scheme) kinetically and sequence preferentially guides the PNA moiety to target a binding site proximal to an A,T region that has an affinity for the minor-groove binder. These results demonstrate a new strategy for constructing DNA recognition ligands composed of a sequence-guiding domain that increases the target specificity and a DNA-modification domain that determines the biological activity of the conjugate. [source]

Synthesis and Biological Evaluation of Distamycin Analogues , New Potential Anticancer Agents

ARCHIV DER PHARMAZIE, Issue 2 2009
Danuta Drozdowska
Abstract Eight of analogues of distamycin, potential minor-groove binders, were synthesized and tested for in-vitro cytotoxicity towards human breast cancer cells MCF-7 and MDA-MB-231. The method of synthesis is simple and convenient. All of the compounds 1,8 showed antiproliferative and cytotoxic effects against both cell lines in the range 3.47 to 12.53 ,M for MDA-MB-231 and 4.35 to 12.66 ,M for MCF-7. All compounds demonstrated activity against DNA topoisomerases I and II at a concentration of 50 ,M. The ethidium bromide assay showed that these compounds bind to plasmid pBR322, yet weaker than distamycin. Further investigations concerning the mechanism of cytotoxicity are now in progress, but the IC50 values suggest that synthetic distamycin analogues with a free amino group, 3,4 and 7,8, can serve as potential carriers of strong acting elements, e. g. alkylating groups. [source]

Sugar,Oligoamides: Bound-State Conformation and DNA Minor-Groove-Binding Description by TR-NOESY and Differential-Frequency Saturation-Transfer-Difference Experiments

CHEMISTRY - A EUROPEAN JOURNAL, Issue 8 2008
Florence Souard
Abstract Selective-frequency saturation-transfer-difference (STD) spectra allow the description of complexes established between minor-groove binders and long tracts of calf thymus DNA (ct-DNA). Two sets of experiments with selective saturation of either the H1, or H4,/H5,/H5,, proton NMR regions of deoxyribose allow the description of the ligand residues close to the inner (H1,) and outer regions (H4,/H5,/H5,,) of the minor groove of double-helical DNA. A series of complexes of sugar,oligoamides (2,6) with ct-DNA have been studied by both TR-NOESY and STD experiments. The binding mode of the complexes is similar to that of netropsin (1) and allows us to define a general binding mode for this family of ligands, in which an NH rim points towards the internal area (inner region) and a CH3 rim points towards the external part (outer region) of the minor groove of DNA. Also by means of both TR-NOESY and STD experiments, a description of the asymmetric centers of the sugar residue close to the inner and outer regions of the groove has been achieved. These results confirm that the sugar is responsible for the differences previously found in binding energetics. [source]