O→S Relay Deprotection: A General Approach to Controllable Donors of Reactive Sulfur Species

Reactive sulfur species (RSS) are biologically important molecules. Among them, H₂S, hydrogen polysulfides (H₂S_n, n>1), persulfides (RSSH), and HSNO are believed to play regulatory roles in sulfur‐related redox biology. However, these molecules are unstable and difficult to handle. Having access to their reliable and controllable precursors (or donors) is the prerequisite for the study of these sulfur species. Reported in this work is the preparation and evaluation of a series of O‐silyl‐mercaptan‐based sulfur‐containing molecules which undergo pH‐ or F^?‐mediated desilylation to release the corresponding H₂S, H₂S_n, RSSH, and HSNO in a controlled fashion. This O→S relay deprotection serves as a general strategy for the design of pH‐ or F^?‐triggered RSS donors. Moreover, we have demonstrated that the O‐silyl groups in the donors could be changed into other protecting groups like esters. This work should allow the development of RSS donors with other activation mechanisms (such as esterase‐activated donors).     

Comparing Hydrogen Deuterium Exchange and Fast Photochemical Oxidation of Proteins: a Structural Characterisation of Wild-Type and ΔN6 β<Subscript>2</Subscript>-Microglobulin

Hydrogen deuterium exchange (HDX) coupled to mass spectrometry (MS) is a well-established technique employed in the field of structural MS to probe the solvent accessibility, dynamics and hydrogen bonding of backbone amides in proteins. By contrast, fast photochemical oxidation of proteins (FPOP) uses hydroxyl radicals, liberated from the photolysis of hydrogen peroxide, to covalently label solvent accessible amino acid side chains on the microsecond-millisecond timescale. Here, we use these two techniques to study the structural and dynamical differences between the protein β₂-microglobulin (β₂m) and its amyloidogenic truncation variant, ΔN6. We show that HDX and FPOP highlight structural/dynamical differences in regions of the proteins, localised to the region surrounding the N-terminal truncation. Further, we demonstrate that, with carefully optimised LC-MS conditions, FPOP data can probe solvent accessibility at the sub-amino acid level, and that these data can be interpreted meaningfully to gain more detailed understanding of the local environment and orientation of the side chains in protein structures.

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Crystal blocking measurements of the time delay of fission induced by 32S, 48Ti, and 58Ni bombardment of W

The time delay in fission induced by bombardment of W with 180 MeV 32S, 240-255 MeV 48Ti, and 315-375 MeV 58Ni has been measured by observation of crystal blocking. There is a clear narrowing and a small increase in the minimum yield of the angular dips for fission compared with scaled dips for elastically scattered ions. This is interpreted as a fission delay of about 2 as, only weakly dependent on energy and atomic number. The delay is longer by 1 to 2 orders of magnitude than obtained from standard interpretations of measurements of prescission neutrons and giant-dipole-resonance gamma rays and from calculations of the nuclear dynamics in heavy-ion reactions.     

Representations of pointed Hopf algebras and their Drinfel'd quantum doubles

We study representations of nontrivial liftings of nilpotent type of quantum linear spaces and their Drinfel'd quantum doubles. We construct a family of Verma-type modules in both cases and prove a parametrization theorem for simple modules. We compute the Loewy and socle series of Verma modules under a mild restriction on the datum of a lifting. We find bases and dimensions of simple modules.     

Level structure of proton-richN=83 Nuclei150Ho and152Tm

The yrast levels of theN=83 odd-odd nuclei¹⁵⁰Ho and¹⁵²Tm have been studied byγ-ray spectroscopy following reactions induced by 240–250 MeV⁶⁰Ni ions. Isomers have been identified in¹⁵⁰Ho at 1.096, 2.625 and ～8.0 MeV and in¹⁵²Tm at 2.555 and ～ 6.3 MeV, and the level schemes of both nuclei have been established up to 2.6 MeV. The level spectra are interpreted using the shell model in terms of the coupling of anf _7/2,h _9/2 or i_13/2 valence neutron to the yrast excitations of the neighboring N=82 nuclei.     

Separation of beta2-microglobulin conformers by high-field asymmetric waveform ion mobility spectrometry (FAIMS) coupled to electrospray ionisation mass spectrometry

An investigation into the use of high-field asymmetric waveform ion mobility spectrometry (FAIMS) coupled to electrospray ionisation mass spectrometry (ESI-MS) for the differentiation of co-populated protein conformers has been conducted on the amyloidogenic protein beta(2)-microglobulin (beta(2)m). Accumulation of beta(2)m in vivo can result in the deposition of insoluble fibrils whose formation is thought to originate from partially folded protein conformers; hence, the folding properties of beta(2)m are of significant interest. We have analysed beta(2)m using ESI-FAIMS-MS under a range of pH conditions and have studied the effect of the ion mobility spectrometry parameters on the behaviour of the various protein conformers. The data show that different protein conformers can be detected and analysed by ESI-FAIMS-MS, the results being consistent with observations of pH denaturation obtained using complementary biophysical techniques. A variant of beta(2)m with different folding characteristics has been analysed for comparison, and the distinctions observed in the data sets for the two proteins are consistent with their folding behaviour. ESI-FAIMS-MS offers significant opportunities for the study of the conformational properties of proteins and thus may present valuable insights into the roles that different conformers play in diseases related to protein folding.