Intact Mass Proteomics Using a Proteoform Atlas.

Top-down proteomics, the characterization of intact proteoforms by tandem mass spectrometry, is the principal method for proteoform characterization in complex samples. Top-down proteomics relies on precursor isolation and subsequent gas-phase fragmentation to make proteoform identifications. While this strategy can produce highly detailed molecular information, the reliance on time-intensive tandem MS limits the speed with which proteoforms can be identified.

Rapid Analysis of Reduced Antibody Drug Conjugate by Online LC-MS/MS with Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.

Antibody drug conjugates (ADCs), which harness the high targeting specificity of monoclonal antibodies (mAb) with the potency of small molecule therapeutics, are one of the fastest growing pharmaceutical classes. Nevertheless, ADC conjugation techniques and processes may introduce intrinsic heterogeneity including primary sequence variants, varied drug-to-antibody ratio (DAR) species, and drug positional isomers, which must be monitored to ensure the safety and efficacy of ADCs. Liquid chromatography coupled to mass spectrometry (LC-MS) is a powerful tool for characterization of ADCs.

Metal-Metal Single Bonds with the Magnetic Anisotropy of Quadruple Bonds: A Systematic Series of Heterobimetallic Bismuth(II)-Rhodium(II) Formamidinate Complexes.

The first set of five heterobimetallic MM'(form) (form=formamidinate) complexes containing a BiRh core has been successfully synthesized. The Bi-Rh bond lengths lie between 2.5196(6) and 2.

Formal Asymmetric Hydrobromination of Styrenes Copper-Catalyzed 1,3-Halogen Migration.

An enantioselective Cu(I)-catalyzed 1,3-halogen migration reaction accomplishes a formal hydrobromination by transferring a bromine activating group from a sp carbon to a benzylic carbon in good and with concomitant borylation of the Ar-Br bond. Computational modelling aids in understanding the reaction outcome and suggests future directions to improve the formal asymmetric hydrobromination. The benzyl bromide can be displaced with a variety of nucleophiles to produce a wide array of functionalized products.

Initial events in bacterial transcription initiation.

Transcription initiation is a highly regulated step of gene expression. Here, we discuss the series of large conformational changes set in motion by initial specific binding of bacterial RNA polymerase (RNAP) to promoter DNA and their relevance for regulation. Bending and wrapping of the upstream duplex facilitates bending of the downstream duplex into the active site cleft, nucleating opening of 13 bp in the cleft.

Chemoenzymatic synthesis of bifunctional polyubiquitin substrates for monitoring ubiquitin chain remodeling.

Covalent attachment of ubiquitin to target proteins is one of the most pervasive post-translational modifications in eukaryotes. Target proteins are often modified with polymeric ubiquitin chains of defined lengths and linkages that may further undergo dynamic changes in composition in response to cellular signals. Biochemical characterization of the enzymes responsible for building and destroying ubiquitin chains is often thwarted by the lack of methods for preparation of the appropriate substrates containing probes for biochemical or biophysical studies.

Ion exchange of protons by coinage metals to give gold and silver encapsulation within a pseudo-D2d distorted face-capped Pd14 cubic kernel: [(μ14-M)Pd22(CO)20(PEt3)8]+ (M = Au, Ag).

Heart of gold (or silver): The pseudo-D2d distorted MPd14 cubic kernel of [(μ14-M)Pd22(CO)20(PEt3)8](+) cations, with M = Au (1), Ag (2), has an encapsulated M atom (see picture; yellow) coordinated to eight cubic corner (black) and six face-capping Pd atoms (gray). Compounds 1 and 2 were obtained (28-60 % yields) from two-step/one-pot reactions of a Pd10 precursor with CF3CO2 H followed by coinage-metal ion exchange of protons.

Oxidation chemistry of axially protected Mo(2) and W(2) quadruply bonded compounds.

Reported is a facile, high-yielding one-pot synthesis of the quadruply bonded ditungsten (II,II) compound W(2)(dpa)(4) (1) (dpa = 2,2'-dipyridylamide), which was obtained from W(CO)(6) at high temperature in naphthalene. A similar reaction in 1,2-dichlorobenzene furnished a ditungsten (III, III) species as the major product that was crystallized as [W(2)(dpa)(3)Cl(2)][BPh(4)] (3). The [W(2)(dpa)(3)Cl(2)](+) cation is better prepared by oxidation of 1 with SO(2)Cl(2).

In situ oligonucleotide synthesis on carbon materials: stable substrates for microarray fabrication.

Glass has become the standard substrate for the preparation of DNA arrays. Typically, glass is modified using silane chemistries to provide an appropriate functional group for nucleic acid synthesis or oligonucleotide immobilization. We have found substantial issues with the stability of these surfaces as manifested in the unwanted release of oligomers from the surface when incubated in aqueous buffers at moderate temperatures.