Sequence-specific alkylation by a tandem motif of pyrrole-imidazole CBI conjugate
نویسندگان
چکیده
منابع مشابه
Targeted suppression of EVI1 oncogene expression by sequence-specific pyrrole-imidazole polyamide.
Human ectopic viral integration site 1 (EVI1) is an oncogenic transcription factor known to play a critical role in many aggressive forms of cancer. Its selective modulation is thought to alter the cancer-specific gene regulatory networks. Pyrrole-imidazole polyamides (PIPs) are a class of small DNA binders that can be designed to target any destined DNA sequence. Herein, we report a sequence-s...
متن کاملTargeting a DNA binding motif of the EVI1 protein by a pyrrole-imidazole polyamide.
The zinc finger protein EVI1 is causally associated with acute myeloid leukemogenesis, and inhibition of its function with a small molecule therapeutic may provide effective therapy for EVI1-expressing leukemias. In this paper we describe the development of a pyrrole-imidazole polyamide to specifically block EVI1 binding to DNA. We first identify essential domains for leukemogenesis through str...
متن کاملA MODEL FOR THE BASIC HELIX- LOOPHELIX MOTIF AND ITS SEQUENCE SPECIFIC RECOGNITION OF DNA
A three dimensional model of the basic Helix-Loop-Helix motif and its sequence specific recognition of DNA is described. The basic-helix I is modeled as a continuous ?-helix because no ?-helix breaking residue is found between the basic region and the first helix. When the basic region of the two peptide monomers are aligned in the successive major groove of the cognate DNA, the hydrophobi...
متن کاملSequence-specific alkylation and cleavage of DNA mediated by purine motif triple helix formation.
An N-bromoacetyl electrophile attached to the 5'-phosphate group of a purine-rich oligonucleotide affords sequence-specific alkylation of duplex DNA (at 37 degrees C, pH 7.4) through the formation of a specific purine.purine.pyrimidine triple-helical complex. In a 645 bp restriction fragment containing three consecutive guanine bases adjacent to the 3'-end of an oligonucleotide binding site, th...
متن کاملAntitumor activity of a pyrrole-imidazole polyamide.
Many cancer therapeutics target DNA and exert cytotoxicity through the induction of DNA damage and inhibition of transcription. We report that a DNA minor groove binding hairpin pyrrole-imidazole (Py-Im) polyamide interferes with RNA polymerase II (RNAP2) activity in cell culture. Polyamide treatment activates p53 signaling in LNCaP prostate cancer cells without detectable DNA damage. Genome-wi...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Nucleic Acids Symposium Series
سال: 2007
ISSN: 0261-3166,1746-8272
DOI: 10.1093/nass/nrm133