Efficient synthesis of azide-bearing cofactor mimics

8-Azido-5'-aziridino-5'-deoxyadenosine (6), a novel cofactor mimic, was synthesized in nine steps from commercially available 2',3'-isopropylideneadenosine in approximately 4% overall yield. Crucial to this success was a very unorthodox phthalimide cleavage procedure, C8 azidation prior to aziridination and late stage alkylation of the 5' amino group with iodoethanol necessitated by the high degree of lability endowed by the aryl azide moiety. Aziridine 6 is envisioned as a useful biochemical tool by which to probe DNA and protein methylation patterns.     

Recent developments in the chemistry of stable silylenes

This paper reviews progress in the field of thermally stable silylenes since 2000. Developments in the synthesis and characterization of new stable silylenes are discussed, followed by a summary of recent theoretical calculations upon model silylenes. The main part of the article concerns the reactivity patterns displayed by silylenes 1-4, which are discussed in terms of their behavior toward radical, organic, inorganic, and organometallic species.     

A polymer scaffold for protein oligomerization

We report the design and synthesis of well-defined polymers for the noncovalent oligomerization of proteins. The reported scaffolds, which were generated by atom-transfer radical polymerization (ATRP), take advantage of the well-characterized interaction between a Ni2+ complex and an oligohistidine sequence (His tag). Thus, our polymers are designed to facilitate the oligomerization of any protein possessing a His tag. We demonstrate that they can oligomerize fibroblast growth factor-8b (FGF-8b) and promote FGF-8b-mediated cell proliferation in the absence of heparin.     

Magnetically-driven biomimetic micro pumping using vortices

Planar micropumps utilizing vortices shed by an oscillating ferromagnetic bar are presented. The movement of the bar is induced by magnetic coupling with an external spinning magnet. Thus, energy transfer is achieved without physical contact or need of any on-chip power source. To create vortices inside the chip, the Reynolds number is locally increased with the oscillation of the bar. The utilization of the vortices as a tool for efficient transfer of energy is inspired by the behaviour of swimming animals and flying insects in nature. The pumps operate in two different scales (milli-scale and micro-scale) in order to take advantage of both. Experiments are presented characterizing the pumps and their flow patterns. The range of operation of the pumps is from 3 microl min(-1) to 600 microl min(-1), though smaller flow rates are also possible.     

Stereoselective total synthesis of antitumor macrolide (+)-rhizoxin D

[structure: see text] A convergent, stereoselective total synthesis of the macrolide antitumor agent rhizoxin D is described. (+)-DIPCl-promoted asymmetric aldol reaction, Evans-Tishchenko 1,3-diol synthesis, modified Julia coupling, and Horner-Wadsworth-Emmons reactions are featured.     

Correlation of ultrasonic scatterer size estimates for the statistical analysis and optimization of angular compounding

Ultrasonic scatterer size estimates generally have large variances due to the inherent noise of spectral estimates used to calculate size. Compounding partially correlated size estimates associated with the same tissue, but produced with data acquired from different angles of incidence, is an effective way to reduce the variance without making dramatic sacrifices in spatial resolution. This work derives theoretical approximations for the correlation between these size estimates, and the coherence between their associated spectral estimates, as functions of ultrasonic system parameters. A Gaussian spatial autocorrelation function is assumed to adequately model scatterer shape. Both approximations compare favorably with simulation results, which consider validation near the focus. Utilization of the correlation/coherence expressions for statistical analysis and optimization is discussed. Approximations, such as the invariance of phase and amplitude terms with angle, are made to obtain closed-form solutions to the derived spectral coherence near the focus and permit analytical optimization analysis. Results indicate that recommended parameter adjustments for performance improvement generally depend upon whether, for the system under consideration, the primary source of change in total coherence with rotation is phase term variation due to the change in the relative position of scattering sites, or field amplitude term variation due to beam movement.     

Molecular simulation of the reversible mechanical unfolding of proteins

In this work we have combined a Wang-Landau sampling scheme [F. Wang and D. Landau, Phys. Rev. Lett. 86, 2050 (2001)] with an expanded ensemble formalism to yield a simple and powerful method for computing potentials of mean force. The new method is implemented to investigate the mechanical deformation of proteins. Comparisons are made with analytical results for simple model systems such as harmonic springs and Rouse chains. The method is then illustrated on a model 15-residue alanine molecule in an implicit solvent. Results for mechanical unfolding of this oligopeptide are compared to those of steered molecular dynamics calculations.     

Statistics of ultrasonic scatterer size estimation with a reference phantom

A theoretical expression for the variance of scatterer size estimates is derived for a modified least squares size estimator used in conjunction with a reference phantom method for backscatter coefficient measurement. A Gaussian spatial autocorrelation function is assumed. Simulations and phantom experiments were performed to verify the results for backscatter and size variances. The dependence of size estimate errors upon free experimental parameters is explored. Implications of the findings for the optimization of scatterer size estimation are discussed. The utility of scatterer size parametric imaging is examined through the signal to noise ratio comparison with standard ultrasonic B-mode imaging.     

Computational studies on the A cluster of acetyl-coenzyme A synthase: geometric and electronic properties of the NiFeC species and mechanistic implications

DFT computational studies on the A cluster of acetyl-coenzyme A synthase are presented and discussed. They aim at evaluating possible A cluster models to settle the ongoing controversy about the nature of the proximal metal site in the catalytically active form of the cluster, recently proposed to be either Ni or Cu. Two possible models for the NiFeC species are considered, [Fe4S4]2+-Ni+CO-Ni2+ and [Fe4S4]2+-Cu+CO-Ni+. While for the former the computed 57Fe, 61Ni, and 13C hyperfine coupling parameters agree reasonably well with corresponding experimental values, for the latter model this agreement is very poor because the actual charge distribution is [Fe4S4]+-Cu+CO-Ni2+. Together, our results provide compelling evidence that the catalytically active A cluster contains Ni rather than Cu at the proximal metal site. Computations on the Ared2 state proposed to be part of the catalytic cycle (Darnault, C.; Volbeda, A.; Kim, E. J.; Legrand, P.; Vernède, X.; Lindahl, P. A.; Fontecilla-Camps, J. C. Nat. Struct. Biol. 2003, 10, 271-279) yield [Fe4S4]+-Ni+-Ni2+, hinting toward a Ni+/Ni3+ redox couple being involved in the methylation reaction.