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Nature has a remarkable ability to carry out site-selective post-translational modification of proteins, therefore enabling a marked increase in their functional diversity.sup.1. Inspired by this, chemical tools have been developed for the synthetic manipulation of protein structure and function, and have become essential to the continued advancement of chemical biology, molecular biology and medicine. However, the number of chemical transformations that are suitable for effective protein functionalization is limited, because the stringent demands inherent to biological systems preclude the applicability of many potential processes.sup.2. These chemical transformations often need to be selective at a single site on a protein, proceed with very fast reaction rates, operate under biologically ambient conditions and should provide homogeneous products with near-perfect conversion.sup.2-7. Although many bioconjugation methods exist at cysteine, lysine and tyrosine, a method targeting a less-explored amino acid would considerably expand the protein functionalization toolbox. Here we report the development of a multifaceted approach to protein functionalization based on chemoselective labelling at methionine residues. By exploiting the electrophilic reactivity of a bespoke hypervalent iodine reagent, the S-Me group in the side chain of methionine can be targeted. The bioconjugation reaction is fast, selective, operates at low-micromolar concentrations and is complementary to existing bioconjugation strategies. Moreover, it produces a protein conjugate that is itself a high-energy intermediate with reactive properties and can serve as a platform for the development of secondary, visible-light-mediated bioorthogonal protein functionalization processes. The merger of these approaches provides a versatile platform for the development of distinct transformations that deliver information-rich protein conjugates directly from the native biomacromolecules.This methionine-selective functionalization strategy uses hypervalent iodine reagents to introduce new groups via the formation of a sulfonium intermediate, which can then undergo further visible-light-mediated reactions to form a diverse range of protein conjugates., Author(s): Michael T. Taylor [sup.1] , Jennifer E. Nelson [sup.1] , Marcos G. Suero [sup.1] , Matthew J. Gaunt [sup.1] Author Affiliations:(1) Department of Chemistry, University of Cambridge, Cambridge, UKMain [...]

Rapid, multiplex identification of pathogens and disease-associated mutations is possible with a new semiconductor biochip. The emergence of pathogens resistant to existing antimicrobial drugs is a growing worldwide health crisis that threatens a return to the pre-antibiotic era. To decrease the overuse of antibiotics, molecular diagnostics systems are needed that can rapidly identify pathogens in a clinical sample and determine the presence of mutations that confer drug resistance at the point of care. We developed a fully integrated, miniaturized semiconductor biochip and closed-tube detection chemistry that performs multiplex nucleic acid amplification and sequence analysis. The approach had a high dynamic range of quantification of microbial load and was able to perform comprehensive mutation analysis on up to 1,000 sequences or strands simultaneously in <2 h. We detected and quantified multiple DNA and RNA respiratory viruses in clinical samples with complete concordance to a commercially available test. We also identified 54 drug-resistance-associated mutations that were present in six genes of Mycobacterium tuberculosis, all of which were confirmed by next-generation sequencing. [ABSTRACT FROM AUTHOR]

The tris(3-isopropylpyrazolyl)methane sulfonate (Tpms(super iPr)) ligand forms octahedral M(Tpms(super iPr))(sub 2) complexes from many divalent metal salts, solvents and stoichiometric ratios, despite the crowded appearance of the isopropyl groups in the crystal structures. The results show that M(Tpms(super iPr))(sub 2) complexes provide a spectroscopic signature for octahedral metals in similar environments and represent the first homologous series of Zn, Cu, Ni, Co and Fe complexes from a ligand with N,N,O donor atoms.

The chemical modification of tryptophan (Trp) has been the subject of interest for nearly 100 years, yet the development of modification conditions that exploit the inherent photolability of Trp has remained elusive. With this perspective, we discuss our recently reported method for Trp photobioconjugation that uses N -carbamoyl pyridinium salts to engage Trp in photoinduced electron transfer. We detail our inspiration and rationale, and we place our report in the context of selected prior art in the field. 1 Introduction 2 Light Activation as a Design Principle in Bioconjugation 3 Targeting Tryptophan with Light 4 Reaction Design and Proof of Concept 5 Mechanistic Considerations 6 Establishing Mechanistic Control 7 Conclusions and Outlook [ABSTRACT FROM AUTHOR]

The different conditions are described for the Rh-catalyzed formation of highly functionalized dihydro- and tetrahydrofuran products via three-component reactions of aldehydes, [alpha]-alkyl-[alpha]-diazoesters and dipolarophiles. The reactions of alkyl-substituted carbonyl ylides have proceeded with regioselectivity and diastereoselectvity that are rationalized in terms of an asynchronous, endo-selective transition state.

The synthesis of 3-tert-butyl-5-methyl-1,2,4-triazole by reaction with KB[H.sub.4] that gave the new potassium tris(3-tert-butyl-5-methyl-1,2,4-triazolyl)borate K(Ttz) ligand is reported. The ligand Ttz is water-soluble with a steric bulk similar to that of tris(pyrazolyl)borate (Tp) and could be made and used in an environmentally friendly manner.

Cell disruptions using ultrasonic energy transmitted through a flexible interface into a liquid region has limitations because the motion of the vibrating tip is not completely transferred into the liquid. To ensure that some degree of contact will be maintained between the ultrasonic horn tip and the flexible interface, the liquid must be pressurized. The pressure conditions that yield consistent coupling between the ultrasonic horn tip and the liquid region were explored in this study by using an analytical model of the system and test fixture experiments. The nature of the interaction between the horn tip and the flexible interface creates pulses of positive pressure rises, increase in temperature, streaming flow, and almost no cavitation in the liquid. There was sufficient energy to create a cloud of microspheres, or beads, that maintain a consistent pattern of ballistic motion in the liquid. The sonication was found to be repeatable by studying video recordings of bead motion and was shown to be statistically consistent using measurements of temperature rise. Sonication of bacterial spores to obtain measurements of released nucleic acid and SEM images of damaged spores were used to verify the effects of liquid pressure on the horn--interface--liquid coupling.