Exploring the limits of benzimidazole DNA-binding oligomers for the hypoxia inducible factor (HIF) site.
The vascular endothelial growth factor (VEGF) and its receptors have been implicated as key-factors in tumor angiogenesis and are major targets in cancer therapy. New oligomers which mimic the architecture of DNA-binding polyamides have been designed to target the hypoxia inducible factor (HIF-1alpha) binding site on the promoter of VEGF gene. These oligomers incorporate an increasing number of six-five fused rings such as hydroxybenzimidazole-imidazole, benzimidazole-pyrrole, benzimidazole-chlorothiophene, and imidazopyridine-pyrrole, and bind the VEGF hypoxia response element (HRE) 5'-TACGT-3' with high affinity and selectivity.
Viger
Anne
A
The Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Dervan
Peter B
PB
D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D018983:DNA Footprinting; D003850:Deoxyribonuclease I / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D020218:Response Elements / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D001562:Benzimidazoles; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009757:Nylons; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004247:DNA; C031000:benzimidazole; D003850:Deoxyribonuclease I