To D or not to D? On estimating the microenvironment polarity of biomolecular cavities

Knowledge of the local polarity of specific cavities in biopolymers can facilitate the design of selective low MW ligands that impact the structure and function of macromolecules. The most common tools for interrogating local polarity are fluorescent probes that are sensitive to their microenvironment. Researchers often evaluate and express this local polarity using dielectric constants, a parameter that reflects an inherent bulk property. A more appropriate expression should take into account solvent-solute interactions at the molecular level. Reevaluation of commonly used fluorophores illustrates the improved correlation between observed Stokes shift changes and E(T)(30) values as compared to the corresponding dielectric constants.     

Cellular uptake of aminoglycosides, guanidinoglycosides, and poly-arginine

Aminoglycosides (including neomycin B and tobramycin) exhibit poor uptake by eukaryotic cell lines. When the amines of these natural products are converted into guanidine groups, their cellular uptake is dramatically enhanced. We have synthesized BODIPY-containing aminoglycosides and guanidinoglycosides to evaluate their cellular uptake properties. Fluorescence activated cell sorting (FACS) and fluorescence microscopy are used to compare the membrane translocation and the cellular localization of these compounds. Upon guanidinylation, the cellular uptake efficiencies of tobramycin and neomycin B are enhanced by 10-fold and 20-fold, respectively. Guanidino-neomycin B exhibits a highly efficient uptake, superior to a fluorescent poly-arginine peptide. Interestingly, the cellular uptake of this common transduction peptide is inhibited by guanidine-neomycin B, suggesting a similar uptake mechanism for both the arginine-rich peptides and the guanidinoglycosides.     

Emissive Synthetic Cofactors: A Highly Responsive NAD+ Analogue Reveals Biomolecular Recognition Features

Apart from its vital function as a redox cofactor, nicotinamide adenine dinucleotide ( NAD⁺ ) has emerged as a crucial substrate for NAD⁺ -consuming enzymes, including poly(ADP-ribosyl)transferase 1 (PARP1) and CD38/CD157. Their association with severe diseases, such as cancer, Alzheimer's disease, and depressions, necessitates the development of new analytical tools based on traceable NAD⁺ surrogates. Here, the synthesis, photophysics and biochemical utilization of an emissive, thieno[3,4-d]pyrimidine-based NAD⁺ surrogate, termed N^thAD⁺ , are described. Its preparation was accomplished by enzymatic conversion of synthetic ^th ATP by nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1). The new NAD⁺ analogue possesses useful photophysical features including redshifted absorption and emission maxima as well as a relatively high quantum yield. Serving as a versatile substrate, N^thAD⁺ was reduced by alcohol dehydrogenase (ADH) to N^thADH and afforded ^thADP-ribose ( ^th ADPr ) upon hydrolysis by NAD⁺ -nucleosidase (NADase). Furthermore, N^thAD⁺ was engaged in cholera toxin A (CTA)-catalyzed mono(^thADP-ribosyl)ation, but was found incapable in promoting PARP1-mediated poly(^thADP-ribosyl)ation. Due to its high photophysical responsiveness, N^thAD⁺ is suited for spectroscopic real-time monitoring. Intriguingly, and as an N7-lacking NAD⁺ surrogate, the thieno-based cofactor showed reduced compatibility (i.e., functional similarity compared to native NAD⁺ ) relative to its isothiazolo-based analogue. The distinct tolerance, displayed by diverse NAD⁺ producing and consuming enzymes, suggests unique biological recognition features and dependency on the purine N7 moiety, which is found to be of importance, if not essential, for PARP1-mediated reactions.     

Dimers of dipyrrometheneboron difluoride (BODIPY) with light spectroscopic applications in chemistry and biology.

A ground-state dimer (denoted D(I)) exhibiting a strong absorption maximum at 477 nm (epsilon = 97 000 M(-1)cm(-1)) can form between adjacent BODIPY groups attached to mutant forms of the protein, plasminogen activator inhibitor type 1 (PAI-1). No fluorescence from excited D(I) was detected. A locally high concentration of BODIPY groups was also achieved by doping lipid phases (micelles, vesicles) with BODIPY-labeled lipids. In addition to an absorption band located at about 480 nm, a new weak absorption band is also observed at ca. 570 nm. Both bands are ascribed to the formation of BODIPY dimers of different conformation (D(I) and D(II)). Contrary to D(I) in PAI-1, the D(II) aggregates absorbing at 570 nm are emitting light observed as a broad band centered at about 630 nm. The integrated absorption band of D(I) is about twice that of the monomer, which is compatible with exciton coupling within a dimer. The F?rster radius of electronic energy transfer between a BODIPY excited monomer and the ground-state dimer (D(I)()) is 57 +/- 2 A. A simple model of exciton coupling suggests that in D(I) two BODIPY groups are stacked on top of each other in a sandwich-like configuration with parallel electronic transition dipoles. For D(II) the model suggests that the S(0) --> S(1) transition dipoles are colinear. An explanation for the previously reported (J. Am. Chem. Soc. 1994, 116, 7801) exceptional light spectroscopic properties of BODIPY is also presented. These are ascribed to the extraordinary electric properties of the BODIPY chromophore. First, changes of the permanent electric dipole moment (Delta(mu) approximately -0.05 D) and polarizability (-26 x 10(-40) C m(2) V(-1)) between the ground and the first excited states are small. Second, the S(0) <--> S(1) electronic transition dipole moments are perpendicular to Delta(mu).     

Investigation of final-stage sintering of various microsize structures prepared by micro powder injection molding

Micro powder injection molding (μPIM) has been developed as a potential technique for mass production of microcomponents in microsystems due to its shaping complexity at low cost, in which sintering is a crucial step to dictate the final properties of the microcomponents. In this paper, final-stage sintering behavior of 316L stainless steel microsize structures prepared by μPIM, φ100 μm and φ60 μm, respectively, was studied. The effect of size reduction in the regime of micrometers on the density of various microsize structures was investigated. Sintering kinetics of the microsize structures of φ100 μm and φ60 μm were studied based on particle level sintering models. It is found that the microsize structures of φ60 μm had higher density than the microsize structures of φ100 μm given the same sintering condition. The results indicate that size reduction in the regime of micrometers facilitated densification of microsize structures. The grain growth mechanism of microsize structures varied with size. Whereas the grain growth of the microsize structures of φ100 μm is governed by surface-diffusion-controlled pore drag, the grain growth of the microsize structures of φ60 μm is controlled by boundary diffusion. During densification, the microsize structures, φ100 μm and φ60 μm, are both controlled by lattice diffusion. The corresponding activation energies are reported in the paper.     

Micro-hot-embossing of 316L stainless steel micro-structures

In this paper, the fabrication of an array of 316L stainless steel cylindrical micro-structures by hot-embossing is studied. The effects of various embossing parameters on the filling of the micro-cavities of silicon mold insert and the demolding of micro-structures are investigated. They include different silicon mold insert configurations, embossing pressure, embossing temperature, embossing time and the thickness of embossing substrate on which the micro-structures stand. Two types of silicon mold insert configurations are investigated. Hot-embossing study with the silicon mold insert attached on the upper mold plate shows that it is not feasible to achieve complete filling. Incomplete filling occurs and increasing the embossing pressure causes excessive thinning of the embossing substrate, so that micro-structures are torn off during demolding. Experiments show that the configuration that the silicon mold insert is positioned flush with lower mold surface improves complete filling. Using suitable embossing pressure and temperature, the larger substrate thickness and longer embossing time ensure the fabrication of defect-free fully filled micro-structures.     

New pairs of -sequences with 4-level cross-correlation

Let ω be a primitive element of GF(2ⁿ), where . Let d=(2^2k+2^s+1-2^k+1-1)/(2^s-1), where n=2k, and s is such that 2s divides k. We prove that the binary m-sequences s(t)=tr(ω^t) and s(dt) have a four-level cross-correlation function and give the distribution of the values.     

Permutation polynomials with low differential uniformity over finite fields of odd characteristic

In this paper, we propose a construction of functions with low differential uniformity based on known perfect nonlinear functions over finite fields of odd characteristic. For an odd prime power q, it is proved that the proposed functions over the finite field Fq are permutations if and only if q≡3(mod 4).     

Codes with the Same Weight Distributions as the Goethals Codes and the Delsarte-Goethals Codes

The Goethals code is a binary nonlinear code of length 2^m+1 which has codewords and minimum Hamming distance 8 for any odd . Recently, Hammons et. al. showed that codes with the same weight distribution can be obtained via the Gray map from a linear code over Z ₄of length 2^m and Lee distance 8. The Gray map of the dual of the corresponding Z ₄ code is a Delsarte-Goethals code. We construct codes over Z ₄ such that their Gray maps lead to codes with the same weight distribution as the Goethals codes and the Delsarte-Goethals codes.