Gene regulation by DNA binding small molecules could have important therapeutic applications. This study reports the investigation of a DNA-binding pyrrole-imidazole polyamide targeted to bind the DNA sequence 5'-WGGWWW-3' with reference to its potency in a subcutaneous xenograft tumor model. The molecule is capable of trafficking to the tumor site following subcutaneous injection and modulates...

While nanocrystalline diamond is quickly becoming one of the most widely studied nanomaterials, achieving a large fraction of diamond nanoparticles in a polymer coating has been an unresolved problem. In this work, polymer nano- and microfibers containing high loadings of 5 nm diamond particles (up to 80 wt % in polyacrylonitrile and 40% in polyamide 11) have been demonstrated using electrospun...

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...

This study intends to establish the mechanical properties of polyamide fiber reinforced shotcrete (PAFRS) in terms of compressive and flexural strengths, in accordance with ASTM C1609/C1609M-12. The mechanical properties identified the influence of polyamide fiber content on the PAFRS strength. This study evaluated the toughness of PAFRS and proposed additional toughness level criteria to bette...

Polyamides are designed oligomers that can bind to DNA in a sequence-specific manner with affinities comparable to those of natural DNA-binding proteins. Recently, an N-terminal 3-chloro-6-fluorobenzothiophene polyamide bound in the minor groove of DNA was co-crystallized at 1.1 Å resolution as an antiparallel dimer. In addition, antimicrobial screenings for this polyamide family and the develo...

Subcutaneous xenografts represent a popular approach to evaluate efficacy of prospective molecular therapeutics in vivo. In the present study, the C-14 labeled radioactive pyrrole-imidazole (Py-Im) polyamide 1, targeted to the 5'-WGWWCW-3' DNA sequence, was evaluated with regard to its uptake properties in subcutaneous xenografts, derived from the human tumor cell lines LNCaP (prostate), A549 (...

Targeting the genome with sequence-specific DNA-binding molecules is a major goal at the interface of chemistry, biology, and precision medicine. Polyamides, composed of N-methylpyrrole and N-methylimidazole monomers, are a class of synthetic molecules that can be rationally designed to "read" specific DNA sequences. However, the impact of different chromatin states on polyamide binding in live...

Polyamide dimers containing three types of aromatic rings-pyrrole, imidazole, and hydroxypyrrole-afford a small-molecule recognition code that discriminates among all four Watson-Crick base pairs in the minor groove. The crystal structure of a specific polyamide dimer-DNA complex establishes the structural basis for distinguishing T.A from A.T base pairs. Specificity for the T.A base pair is ac...

The use of non-metal clasp denture (NMCD) materials may seriously affect the remaining tissues because of the low rigidity of NMCD materials such as polyamides. The purpose of this study was to develop a high-rigidity glass fiber-reinforced thermoplastic (GFRTP) composed of E-glass fiber and polyamide-6 for NMCDs using an injection molding. The reinforcing effects of fiber on the flexural prope...