Looking glass mechanism-based inhibition of peptidylglycine α-amidating monooxygenase

Carboxyl-terminal amidation, a required post-translational modification for the bioactivation of many peptide hormones, entails sequential enzymatic action by peptidylglycine α-monooxygenase (PAM, EC 1.14.17.3) and peptidylamidoglycolate lyase (PGL, EC 4.3.2.5). We have previously demonstrated that PAM and PGL exhibit strict tandem reaction stereospecificities, with PAM producing exclusively α-hydroxyglycine moieties of absolute configuration (S), and PGL being reactive only toward (S)-α-hydroxyglycines, and we have also shown that PAM exhibits strict P₂-subsite stereospecificity toward both peptide substrates and peptidyl competitive inhibitors. Herein, it is reported that the inhibitory stereochemistry of olefinic mechanism-based amidation inhibitors differs from the strict subsite stereospecificity exhibited by PAM toward substrates and reversible competitive inhibitors. Kinetic analyses of mechanism-based irreversible inhibition of PAM by the (S)- and (R)-enantiomers of 5-acetamido-4-oxo-6-phenyl-2-hexenoic acid were carried out using the rigorous progress curve method. The two enantiomers were found to exhibit very similar values of K_I and k_inact and in both cases kinetic analysis confirmed that irreversible inhibition occurs strictly at the substrate binding site with no ESI complex being formed during the catalytic processing of these irreversible inhibitors. Molecular docking studies were carried out to help rationalize the sharp contrast in the stereospecificity of PAM toward irreversible inhibitors versus substrates and competitive inhibitors. The results revealed that, in contrast to substrates, both docked enantiomers of the olefinic irreversible inhibitors are well-positioned to undergo catalytic processing at the Cu center that gives rise to irreversible inhibition. Taken together, these results provide one of the first clear examples where the stereospecificity of a particular enzyme toward mechanism-based irreversible inhibitors differs from that for substrates and competitive inhibitors.     

Traffic noise reduction due to the screening effect of balconies on a building façade

In this paper we discuss the use of self-protecting buildings as a means of reducing traffic noise nuisance. The results obtained from a computer model of one self-protecting configuration, namely a closed balcony shielding a window into a room, are compared with measurements made on a 1:10 scale model of this situation. From a comparison of these results an empirical equation is given which permits the benefits of a closed balcony to be predicted from the application of standard noise screen formulae.Since the degree of annoyance experienced by people exposed to traffic noise has been shown to be influenced by temporal variations of level, the computer model was extended to enable the effect of the balcony on this variability to be assessed.     

A general solution of the diffusion equation for semiinfinite geometries

The solution of the time-dependent diffusion equation in a semiinfinite planar, cylindrical, or spherical geometry with common initial and asymptotic boundary conditions is considered. It is shown that this boundary value problem may be described by a single equation which involves only a first order spatial derivative and a half order time derivative. The replacement is exact in the planar and spherical geometry cases but approximate in the cylindrical case. This replacement permits the solution of the original boundary value problem to be written for any boundary condition at the origin. It also leads to a simple relationship between the boundary flux and the boundary intensive variable, which does not require a calculation of the intensive variable at all positions and times.     

The inhibition of factor inhibiting hypoxia-inducible factor (FIH) by beta-oxocarboxylic acids

Cyclic beta-oxocarboxylic acids inhibit factor inhibiting hypoxia-inducible factor via ligation to the active site iron.     

How does a reversible electrode respond in a.c. voltammetry? Part 2: solutions for the periodic current amplitudes

Journal of Solid State Electrochemistry - In a.c. voltammetry, a programmed electrical potential—a linear ramp modulated by a sine wave of frequency ω and modest amplitude—is...     

Ultra‐Fast Degradation of Chemical Warfare Agents Using MOF–Nanofiber Kebabs

The threat associated with chemical warfare agents (CWAs) motivates the development of new materials to provide enhanced protection with a reduced burden. Metal–organic frame‐works (MOFs) have recently been shown as highly effective catalysts for detoxifying CWAs, but challenges still remain for integrating MOFs into functional filter media and/or protective garments. Herein, we report a series of MOF–nanofiber kebab structures for fast degradation of CWAs. We found TiO₂ coatings deposited via atomic layer deposition (ALD) onto polyamide‐6 nanofibers enable the formation of conformal Zr‐based MOF thin films including UiO‐66, UiO‐66‐NH₂, and UiO‐67. Cross‐sectional TEM images show that these MOF crystals nucleate and grow directly on and around the nanofibers, with strong attachment to the substrates. These MOF‐functionalized nanofibers exhibit excellent reactivity for detoxifying CWAs. The half‐lives of a CWA simulant compound and nerve agent soman (GD) are as short as 7.3 min and 2.3 min, respectively. These results therefore provide the earliest report of MOF–nanofiber textile composites capable of ultra‐fast degradation of CWAs.     

Multi-scan cyclic voltammetry of a solution containing mixed valence states

Journal of Solid State Electrochemistry - When both members of a redox pair are present in a voltammetric cell, the applied signal must start at the null potential if pure cyclic voltammetry is to...     

A new technique for the 14 MeV neutron activation analysis of sodium and potassium

Cerenkov radiation produced in perspex by β and γ emitters may be readily measured by counting in the tritium channel of a liquid scintillation spectrometer, a technique which has interesting applications in neutron activation analysis. Further the fact that there are often considerable variations in the β energies of different radionuclides produced by activation means that by the use of suitable absorbers the determination of isotopes in a mixture is frequently possible. Such a method has been applied in the determination of a mixture of sodium and potassium. At the same time sensitivities and detection limits of the other alkali elements have been investigated and compared with results obtained from conventional gamma spectral analysis. Using such a technique it has proved possible to effect a considerable increase in sensitivity for the determination of sodium and potassium.     

Pitfalls in the application of statistics to chemical data: the determination of the partition ratio $$K_{\mathrm{ow} }$$ as a case in point

Nowadays those who make replicate measurements of physicochemical properties usually employ spreadsheets or handheld devices to perform averaging and other statistical operations. Using the determination of a partition ratio as an exemplary procedure, and employing statistical simulation, we examine errors that can arise by unthinking reliance on “clicking”. Alternative, more soundly based, procedures are advocated. A serendipitous result is that the logarithm of a partition ratio behaves statistically much better than expected.