Phosphate anion chelation and base-pairing. Design of receptors and carriers for nucleotides and nucleotide analogues

Abstract

A rational approach to the development of effective carriers for the through-membrane transport of GMP (guanosine 5′-monophosphate) at neutral pH is described. The approach detailed is a ditopic one predicated on the use of nucleic acid-base ‘nucleobase’ subunits to provide stabilizing hydrogen bonding interactions and the use of expanded porphyrin anion binding subunits to provide phosphate chelation. Appropriate background studies along with the synthesis of a functioning state-of-the-art system are reported. In addition, the reasons for preparing such GMP transport systems are presented in full.     

Biomimetic Synthesis of Materials for Technology

In a world with ever decreasing natural reserves, researchers are striving to find sustainable methods of producing components for technology. Bioinspired, biokleptic and biomimetic materials can be used to form a wide range of technologically relevant materials under environmentally friendly conditions. Here we investigate a range of biotemplated and bioinspired materials that can be used to develop components for devices, such as optics, photonics, photovoltaics, circuits and data storage.     

High dynamic range proteome imaging with the structured illumination gel imager

A current challenge for proteomics is detecting proteins over the large concentration ranges found in complex biological samples such as whole‐cell extracts. Currently, no unbiased, whole‐proteome analysis scheme is capable of detecting the full range of cellular proteins. This is due in part to the limited dynamic range of the detectors used to sense proteins or peptides. We present a new technology, structured illumination (SI) gel imager, which detects fluorescently labeled proteins in electrophoretic gels over a 1 000 000‐fold concentration range. SI uses computer‐generated masks to attenuate the illumination of highly abundant proteins, allowing for long exposures of low‐abundance proteins, thus avoiding detector saturation. A series of progressively masked gel images are assembled into a single, very high dynamic range image. We demonstrate that the SI imager can detect proteins over a concentration range of approximately 1 000 000‐fold, making it a useful tool for comprehensive, unbiased proteome‐wide surveys.     

Synthetic studies directed toward the AB decalin common to HMP-Y1 and hibarimicinone

Efforts toward the synthesis of the decalin ring system common to the hibarimicin shunt metabolite HMP-Y1 and parent aglycone hibarimicinone are reported herein. An intramolecular Diels–Alder cyclization rapidly generated the decalin framework. Two approaches toward completion of the AB decalin were vetted. Incorporation of a phenylsulfonyl leaving group β- to both a ketone and a γ-lactone followed by base-induced elimination of sulfinate led to the undesired α,β-unsaturated lactone. Methanolysis of the γ-lactone followed by elimination produced the unexpected bridged cyclic ether by way of an intramolecular oxy-Michael addition of the endo oriented C13 alcohol.     

An appraisal of the Suzuki cross-coupling reaction for the synthesis of novel fluorescent coumarin derivatives

We report the chemical design and development of 3-aryl-substituted 7-alkoxy-4-methylcoumarins with enhanced fluorogenic properties. The 3-aryl substituents are installed via an optimized Suzuki–Miyaura cross-coupling (SMC) reaction between a 7-alkoxy-3-bromo-4-methylcoumarin and aryl boronic MIDA esters using Pd(OAc)₂/XPhos in a catalytic system with K₂CO₃ in aqueous THF. Under these conditions, an exocyclic ester functionality is found to be unaffected. Subsequent saponification revealed a carboxylic acid functionality that is suitable for conjugation reactions. Evaluation of their fluorescence properties indicated that the installed 3-heteroaryl substituent, particularly benzofuran-2-yl, resulted in a significant red shift of both the excitation and emission wavelengths.     

Application of capillary electrophoresis for the early diagnosis of cancer

Early diagnosis is the key to the effective treatment of cancer. The detection of cancer biomarkers plays a critical role not only in cancer early diagnosis, but also in classification and staging tumor progression, or assessment prognosis and treatment response. Currently, various molecular diagnostic techniques have been developed for cancer biomarker studies, with many of the more effective approaches requiring a separation step before detection. Capillary electrophoresis (CE) can perform rapid and efficient separation with small samples, which is well-suited for analysis of both small- and macro- molecule biomarkers in complex samples. CE has different separation modes and can couple to different detectors into a variety of platforms, such as conducting studies on DNA/ RNA point mutation, protein misexpression, and metabolite abnormality. Similarly, microchip capillary electrophoresis (MCE) appears as a very important biomarker screening platform with the merits of high throughput, integration, and miniaturization, which makes it a promising clinical tool. By hyphenated different detectors, or integrated with immunoassay, PCR/LDR and related technologies, MCE can be constructed into diverse platforms used in genomics, proteomics, and metabolomics study for biomarkers discovery. The multiplex biomarker screening approach via CE- or MCE-based platforms is becoming a trend. This paper focuses on studies of cancer biomarkers via CE/MCE platforms, based on the studies published over the past 3 years. Some recent CE applications in the field of cancer study, such as cancer theranostics, are introduced.     

Loop-quantum-gravity vertex amplitude

Spin foam models are hoped to provide the dynamics of loop-quantum gravity. However, the most popular of these, the Barrett-Crane model, does not have the good boundary state space and there are indications that it fails to yield good low-energy n-point functions. We present an alternative dynamics that can be derived as a quantization of a Regge discretization of Euclidean general relativity, where second class constraints are imposed weakly. Its state space matches the SO(3) loop gravity one and it yields an SO(4)-covariant vertex amplitude for Euclidean loop gravity.