Epigenetic modifications that govern the gene expression are often overlooked with the design of artificial genetic switches. N-Methylpyrrole-N-methylimidazole (PI) hairpin polyamides are programmable small DNA binding molecules that have been studied in the context of gene regulation. Recently, we synthesized a library of compounds by conjugating PI polyamides with SAHA, a chromatin-modifier. ...

The Nucleosome Core Particle (NCP) is the minimal unit in eukaryotic chromatin and a unique target for DNA-binding polyamides. The ability to modulate the stability of nucleosomes would be a useful tool for molecular biology and gene regulation. A series of polyamide clamps designed to differentiate between the NCP and B-form DNA were synthesized and analyzed using DNase I footprinting. In addi...

BACKGROUND Gene-specific targeting of any protein-DNA complex by small molecules is a challenging goal at the interface of chemistry and biology. Polyamides containing N-methylimidazole and N-methylpyrrole amino acids are synthetic ligands that have an affinity and specificity for DNA comparable to many naturally occurring DNA-binding proteins. It has been shown that an eight-ring hairpin polya...

Aberrant overexpression of ERG induced by the TMPRSS2-ERG gene fusion is likely involved in the development of prostate cancer. Synthetic pyrrole-imidazole (PI) polyamides recognize and attach to the minor groove of DNA with high affinity and specificity. In the present study, we designed a PI polyamide targeting TMPRSS2-ERG translocation breakpoints and assessed its effect on human prostate ca...

BACKGROUND Antibiotics are biocides or products that inhibit the growth of microorganisms in the living cells and there are extensive works directed to develop efficient antimicrobial agents. The sulfonamide-containing polymers have great potential to resist gram-positive or gram-negative bacterial and fungal attacks. As a therapeutic agent, the sulfonamides have been reported as antitumor and ...

Two series of novel aromatic polyamides containing pendent dimethyltriphenylamine moieties were prepared based on N,N-bis(4-aminophenyl)-N′,N′-di(4-methylphenyl)-1,4-phenylenediamine (4) and N,Nbis(4-carboxyphenyl)-N′,N′-di(4-methylphenyl)-1,4-phenylenediamine (4′). These compounds with similar structures were successfully synthesized by amination reactions of 4-amino-4′,4′′-dimethyltriphenylam...

The characterization of a new class of pyrrole-imidazole hairpin polyamides with beta-amino-gamma-turn units for recognition of the DNA minor groove is reported. A library of eight hairpins containing ( R)- and ( S)-3,4-diaminobutyric acid (beta-amino-gamma-turn) has been synthesized, and the impact of the molecules on DNA-duplex stabilization was studied for comparison with the parent gamma-am...

Development of sequence-reading polyamides or "lexitropsins" with comparable DNA-binding affinities to cellular proteins raises the possibility of artificially regulated gene expression. Covalent linkage of polyamide ligands, with either a hairpin motif or crosslinking methylene bridge, has greatly improved binding affinity by ensuring their side-by-side register. Whereas hairpin polyamides hav...