Antitumor activity of vanadocene Y and its selenocyanate derivative in xenografted caki-1 tumors in mice

The para-methoxybenzyl-substituted vanadocene dichloride (Vanadocene Y) (1) and its diselenocyanate (Selenocyanato-Vanadocene Y) (2) were tested in vitro in an anti-angiogenesis assay against human umbilical vein endothelial cells (HUVEC) delivering IC50 values of 0.92 ± 0.03 μM (1) and 37 ± 11 μM (2). In a cytotoxicity assay against the human renal cancer cells, CAKI-1, the compounds demonstrated IC50 values of 0.55 ± 0.09 μM (1) and 0.25 ± 0.03 μM (2). Then both compounds were given at their maximum tolerable dose, MTD, of 20 mg/kg/d (1) or 40 mg/kg/d (2) on four consecutive days or at 50% of the MTD on five consecutive days per week for three weeks to overall four cohorts of eight CAKI-1 tumor-bearing female NMRI:nu/nu mice each, while a further cohort was treated with solvent only. Both MTD-treated mouse cohorts showed a statistically significant tumor growth reduction with respect to the solvent-treated control group with an optimal T/C value of 47% on day 39 of the experiment. Immunohistological analysis revealed that the expression of the proliferation marker Ki-67 was reduced due to long-term treatment with 2.     

Use of quantum dots in the development of assays for cancer biomarkers

Biomarker assays may be useful for screening and diagnosis of cancer if a set of molecular markers can be quantified and statistically differentiated between cancerous cells and healthy cells. Markers of disease are often present at very low concentrations, so methods capable of low detection limits are required. Quantum dots (QDs) are nanoparticles that are emerging as promising probes for ultrasensitive detection of cancer biomarkers. QDs attached to antibodies, aptamers, oligonucleotides, or peptides can be used to target cancer markers. Their fluorescent properties have enabled QDs to be used as labels for in-vitro assays to quantify biomarkers, and they have been investigated as in-vivo imaging agents. QDs can be used as donors in assays involving fluorescence resonance energy transfer (FRET), or as acceptors in bioluminescence resonance energy transfer (BRET). The nanoparticles are also capable of electrochemical detection and are potentially useful for “lab-on-a-chip” applications. Recent developments in silicon QDs, non-blinking QDs, and QDs with reduced-size and controlled-valence further make these QDs bioanalytically attractive because of their low toxicity, biocompatibility, high quantum yields, and diverse surface modification flexibility. The potential of multiplexed sensing using QDs with different wavelengths of emission is promising for simultaneous detection of multiple biomarkers of disease.

Discrete Uncertainty Principles and Sparse Signal Processing

We develop new discrete uncertainty principles in terms of numerical sparsity, which is a continuous proxy for the 0-norm. Unlike traditional sparsity, the continuity of numerical sparsity naturally accommodates functions which are nearly sparse. After studying these principles and the functions that achieve exact or near equality in them, we identify certain consequences in a number of sparse signal processing applications.     

Concise and enantioselective synthesis of Fmoc-Pmp(But)2-OH and design of potent Pmp-containing Grb2-SH2 domain antagonists

[reaction: see text] L-Phosphonomethylphenylalanine (L-Pmp) is an important phosphatase-resistant pTyr analogue. A most concise and stereoselective approach to the synthesis of the suitably protected Fmoc-Pmp(Bu(t))(2)-OH was developed in order to incorporate the functionally significant L-Pmp residue into peptides and peptidomimetics efficiently using standard Fmoc protocol. With this key building block, we are able to efficiently synthesize a series of potent Pmp-containing Grb2-SH2 domain antagonists, which can be used as chemotherapeutic leads for the treatment of erbB2-overexpressed breast cancer.     

Novel antibiotics: macrocyclic peptides designed to trap Holliday junctions

[reaction: see text] Described are the syntheses of eight macrocyclic peptides designed to trap Holliday junctions in bacteria, thereby inhibiting bacterial growth. These macrocycles were designed from linear dimerized hexapeptides that bind to the C-2 symmetrical Holliday junction. They were synthesized from three monomers using a combinatorial-like strategy that permits elucidation of the monomer role in accumulation of Holliday junctions and antibiotic activity. These macrocycles are an important step in designing and synthesizing a new class of antibiotics.     

The chemical ‘Knight’s Move’ relationship: what is its significance?

Similarities in properties among pairs of metallic elements and their compounds in the lower-right quadrant of the Periodic Table have been named the ‘Knight’s Move’ relationship. Here, we have undertaken a systematic study of the only two ‘double-pairs’ of ‘Knight’s Move’ elements within this region: copper-indium/indium-bismuth and zinc-tin/tin-polonium, focussing on: metal melting points; formulas and properties of compounds; and melting points of halides and chalcogenides. On the basis of these comparisons, we conclude that the systematic evidence for ‘Knight’s Move’ relationships derives from similarities in formulas and properties of matching pairs of compounds in the same oxidation state. Physical properties, such as melting points, do not provide consistent patterns and trends and hence should not be considered as a common characteristic of this relationship.     

Preparation and characterization of implantable sensors with nitric oxide release coatings

The widespread use of miniaturized chemical sensors to monitor clinically important analytes such as PO₂, PCO₂, pH, electrolytes, glucose and lactate in a continuous, real-time manner has been seriously hindered by the erratic analytical results often obtained when such devices are implanted in vivo. One major factor that has influenced the analytical performance of indwelling sensors is the biological response they elicit when in contact with blood or tissue (e.g. thrombus formation on the device surface, inflammatory response, encapsulation, etc.). Nitric oxide (NO) has been shown to be a potent inhibitor of platelet adhesion and activation as well as a promoter of wound healing in tissue. Herein, we review recent work aimed at the development of hydrophobic NO-releasing polymers that can be employed to coat catheter-type amperometric oxygen sensors without interfering with the analytical performance of these devices. Such modified sensors are shown to exhibit greatly enhanced hemocompatibility and improved analytical performance when implanted within porcine carotid and femoral arteries for up to 16 h. Further, results from preliminary studies also demonstrate that prototype fluorescent oxygen sensors, catheter-style potentiometric carbon dioxide sensors and subcutaneous needle-type enzyme-based amperometric glucose sensors can also be fabricated with new NO-release outer coatings without compromising the analytical response characteristics of these devices. The NO-release strategy may provide a solution to the lingering biocompatibility problems encountered when miniature chemical sensors are implanted in vivo.     

Functional and tuneable amino acid polymers prepared by RAFT polymerization

We report the application of reversible addition‐fragmentation chain transfer polymerization using a novel chain transfer agent toward the synthesis of a variety of copolymers containing proline‐derived monomeric units. This methodology enables ready access to a number of polymeric species with narrow molecular weight distributions, reliable functional unit incorporations, and high conversions. The methodology is also a facile approach to novel copolymeric species incorporating amino acids, which possess unique material properties and the potential for further organocatalytic application. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2009     

Perron Conditions for Uniform Exponential Expansiveness of Linear Skew-Product Flows

 We present necessary and sufficient conditions for uniform exponential expansiveness of discrete skew-product flows, in terms of uniform complete admissibility of the pair (c ₀(N, X), c ₀(N, X)). We give discrete and continuous characterizations for uniform exponential expansiveness of linear skew-product flows, using the uniform complete admissibility of the pairs (c ₀(N, X), c ₀(N, X)) and (C ₀(R ₊, X), C ₀(R ₊, X)), respectively. We generalize an expansiveness theorem due to Van Minh, R?biger and Schnaubelt, for the case of linear skew-product flows.