Cyclic pyrrole-imidazole polyamides targeted to the androgen response element

Hairpin pyrrole−imidazole (Py-Im) polyamides are a class of cell-permeable DNA-binding small molecules that can disrupt transcription factor−DNA binding and regulate endogenous gene expression. The covalent linkage of antiparallel Py-Im ring pairs with an γ-amino acid turn unit affords the classical hairpin Py-Im polyamide structure. Closing the hairpin with a second turn unit yields a cyclic polyamide, a lesser-studied architecture mainly attributable to synthetic inaccessibility. We have applied our methodology for solution-phase polyamide synthesis to cyclic polyamides with an improved high-yield cyclization step. Cyclic 8-ring Py-Im polyamides 1−3 target the DNA sequence 5′-WGWWCW-3′, which corresponds to the androgen response element (ARE) bound by the androgen receptor transcription factor to modulate gene expression. We find that cyclic Py-Im polyamides 1−3 bind DNA with exceptionally high affinities and regulate the expression of AR target genes in cell culture studies, from which we infer that the cycle is cell permeable

Equation of state for Entanglement in a Fermi gas

Entanglement distance is the maximal separation between two entangled electrons in a degenerate electron gas. Beyond that distance, all entanglement disappears. We relate entanglement distance to degeneracy pressure both for extreme relativistic and non-relativistic systems, and estimate the entanglement distance in a white dwarf. Treating entanglement as a thermodynamical quantity, we relate the entropy of formation and concurrence to relative electron distance, pressure, and temperature, to form a new equation of state for entanglement.Comment: To appear in Phys. Rev. A., 4 pages, 1 figur

Optimized Synthesis and Structural Characterization of the Borosilicate MCM-70

A structure analysis of the borosilicate zeolite MCM-70, whose synthesis had been patented in 2003, was reported in 2005. Unfortunately, that structure analysis was somewhat ambiguous. Anisotropic line broadening made it difficult to model the peak shape, some peaks in the electron density map could not be interpreted satisfactorily, the framework geometry was distorted, and MAS NMR results were partially contradictory. In an attempt to resolve some of these points, an optimization of the synthesis was undertaken, and the structure was reinvestigated. The structure was solved from synchrotron powder diffraction data collected on an as-synthesized sample (Pmn2_1, a = 13.3167(1) Å, b = 4.6604(1) Å, c = 8.7000(1) Å) using a powder charge-flipping algorithm. The framework topology, with a 1-dimensional, 10-ring channel system, is identical to the one previously reported. However, the B in this new sample was found to be ordered in the framework, fully occupying one of the four tetrahedral sites. Two extra-framework K^+ ion positions, each coordinated to five framework O atoms and one water molecule, were also found. The solid state ^(29)Si, ^(11)B and ^1H NMR results are fully consistent with this ordered structure

Electrophoresis of colloidal dispersions in the low-salt regime

We study the electrophoretic mobility of spherical charged colloids in a low-salt suspension as a function of the colloidal concentration. Using an effective particle charge and a reduced screening parameter, we map the data for systems with different particle charges and sizes, including numerical simulation data with full electrostatics and hydrodynamics and experimental data for latex dispersions, on a single master curve. We observe two different volume fraction-dependent regimes for the electrophoretic mobility that can be explained in terms of the static properties of the ionic double layer.Comment: Substantially revised versio