A General Synthesis of C8-Arylpurine Phosphoramidites

A general scheme for the synthesis of C8-arylpurine phosphoramidites has been developed. C8-Arylation of C8-bromo-2′-deoxyguanosine is the key step and has been achieved through the use of a Suzuki coupling. Since the coupling reaction is conducted under aqueous conditions, it is unnecessary to protect and then deprotect the hydroxyl groups, thus saving several steps and improving overall yields. Once the C8-arylgroup is introduced, the glycosidic bond becomes very sensitive to acid catalyzed cleavage. Protection of the amino groups as the corresponding N,N-dimethylformamidine derivative improves stability of the derivatives. Synthetic C8-arylpurines were successfully used to prepare synthetic oligonucleotides

A General Synthesis of C8-Arylpurine Phosphoramidite

A general scheme for the synthesis of C8-arylpurine phosphoramidites has been developed. C8-Arylation of C8-bromo-2′-deoxyguanosine is the key step and has been achieved through the use of a Suzuki coupling. Since the coupling reaction is conducted under aqueous conditions, it is unnecessary to protect and then deprotect the hydroxyl groups, thus saving several steps and improving overall yields. Once the C8-arylgroup is introduced, the glycosidic bond becomes very sensitive to acid catalyzed cleavage. Protection of the amino groups as the corresponding N,N-dimethylformamidine derivative improves stability of the derivatives. Synthetic C8-arylpurines were successfully used to prepare synthetic oligonucleotides

An investigation into the feasibility of myoglobin-based single-electron transistors

Myoglobin single-electron transistors were investigated using nanometer- gap platinum electrodes fabricated by electromigration at cryogenic temperatures. Apomyoglobin (myoglobin without heme group) was used as a reference. The results suggest single electron transport is mediated by resonant tunneling with the electronic and vibrational levels of the heme group in a single protein. They also represent a proof-of-principle that proteins with redox centers across nanometer-gap electrodes can be utilized to fabricate single-electron transistors. The protein orientation and conformation may significantly affect the conductance of these devices. Future improvements in device reproducibility and yield will require control of these factors

Just Care: Learning From and With Graduate Students in a Doctor of Nursing Practice Program

In 2010, Fairfield University, a Jesuit Carnegie Masters Level 1 University located in the Northeast, established its first doctoral -level program: the Doctorate of Nursing Practice (DNP). In a developing program such as the DNP, some of the most pressing concerns of current rhetoric and writing in the disciplines align and interact with the education of clinical nurse leaders — questions of transfer, ethical practice, reflection, assignment desi gn, and community engagement. Clearly, nursing scholar/practitioners and writing scholar/practitioners have much to offer and to learn from each other. In this article, we trace the initial action -research undertaken by the School of Nursing, the Writing C enter, and the Center for Academic Excellence to document, reflect upon, and support the reading and writing experiences of DNP graduate students as they negotiate the new curriculum

Src Binds Cortactin Through An Sh2 Domain Cystine-Mediated Linkage

Tyrosine-kinase-based signal transduction mediated by modular protein domains is critical for cellular function. The Src homology (SH)2 domain is an important conductor of intracellular signaling that binds to phosphorylated tyrosines on acceptor proteins, producing molecular complexes responsible for signal relay. Cortactin is a cytoskeletal protein and tyrosine kinase substrate that regulates actin-based motility through interactions with SH2-domain-containing proteins. The Src kinase SH2 domain mediates cortactin binding and tyrosine phosphorylation, but how Src interacts with cortactin is unknown. Here we demonstrate that Src binds cortactin through cystine bonding between Src C185 in the SH2 domain within the phosphotyrosine binding pocket and cortactin C112/246 in the cortactin repeats domain, independent of tyrosine phosphorylation. Interaction studies show that the presence of reducing agents ablates Src-cortactin binding, eliminates cortactin phosphorylation by Src, and prevents Src SH2 domain binding to cortactin. Tandem MS/MS sequencing demonstrates cystine bond formation between Src C185 and cortactin C112/246. Mutational studies indicate that an intact cystine binding interface is required for Src-mediated cortactin phosphorylation, cell migration, and pre-invadopodia formation. Our results identify a novel phosphotyrosine-independent binding mode between the Src SH2 domain and cortactin. Besides Src, one quarter of all SH2 domains contain cysteines at or near the analogous Src C185 position. This provides a potential alternative mechanism to tyrosine phosphorylation for cysteine-containing SH2 domains to bind cognate ligands that may be widespread in propagating signals regulating diverse cellular functions

Application of Hansch’s Model to Capsaicinoids and Capsinoids: A Study Using the Quantitative Structure−Activity Relationship. A Novel Method for the Synthesis of Capsinoids

We describe a synthetic approach for two families of compounds, the capsaicinoids and capsinoids, as part of a study of the quantitative relationship between structure and activity

Chemical Properties of Element 105 in Aqueous Solution: Halide Complex Formation and Anion Exchange into Triisoctyl Amine

Studies of the halide complexation of element 105 in aqueous solution were performed on 34-s 262Ha produced in the 249Bk(18-O,5n) reaction. The 262Ha was detected by measuring the fission and alpha activities associated with its decay and the alpha decays of its daughter, 4.3-s 258Lr. Time-correlated pairs of parent and daughter alpha particles provided a unique identification of the presence of 262Ha. About 1600 anion exchange separations of 262Ha from HCl and mixed HC1/HF solutions were performed on a one-minute time scale. Reversed-phase micro-chromatographic columns incorporating triisooctyl amine (TIOA) on an inert support were used in the computer-controlled liquid chromatography apparatus, ARCA II. 262Ha was shown to be adsorbed on the column from either 12 M HCl/0.02 M HF or 10 M HCl solutions like its homologs Nb and Ta, and like Pa. In elutions with 4 M HCl/0.02 M HF (Pa-Nb fraction), and with 6 M HNO3/O.OI5 M HF (Ta fraction), the 262Ha activity was found in the Pa-Nb fraction showing that the anionic halide complexes are different from those of Ta, and are more like those of Nb and Pa. In separate elutions with 10 M HCl/0.025 M HF (Pa fraction) and 6 M HN03/0.015 M HF (stripping of Nb) the 262Ha was found to be equally divided between the Pa and Nb fractions. The non-tantalum like halide complexation of Ha is indicative of the formation of oxohalide or hydroxohalide complexes, like [NbOCU]" and [PaOCl4] or [Pa(OH)2Cl4]", at least for intermediate HCl concentrations, in contrast to the pure halide complexes in Ta, like [TaCl6]-

Rigid spin-labeled nucleoside Ç: a nonperturbing EPR probe of nucleic acid conformation

Rigid spin-labeled nucleoside Ç, an analog of deoxycytidine that base-pairs with deoxyguanosine, was incorporated into DNA oligomers by chemical synthesis. Thermal denaturation experiments and circular dichroism (CD) measurements showed that Ç has a negligible effect on DNA duplex stability and conformation. Nucleoside Ç was incorporated into several positions within single-stranded DNA oligomers that can adopt two hairpin conformations of similar energy, each of which contains a four-base loop. The relative mobility of nucleotides in the alternating C/G hairpin loops, 5′-d(GCGC) and 5′-d(CGCG), was determined by electron paramagnetic resonance (EPR) spectroscopy. The most mobile nucleotide in the loop is the second one from the 5′-end, followed by the third, first and fourth nucleotides, consistent with previous NMR studies of DNA hairpin loops of different sequences. The EPR hairpin data were also corroborated by fluorescence spectroscopy using oligomers containing reduced Ç (Çf), which is fluorescent. Furthermore, EPR spectra of duplex DNAs that contained Ç at the end of the helix showed features that indicated dipolar coupling between two spins. These data are consistent with end-to-end duplex stacking in solution, which was only observed when G was paired to Ç, but not when Ç was paired with A, C or T