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Epithelial sodium channels (ENaC) are processed by proteases as they transit the biosynthetic pathway. We recently observed that furin-dependent processing of the [alpha]-subunit of ENaC at two sites within its extracellular domain is required for channel activation due to release of a 26-residue inhibitory domain. While channels with [alpha]-subunits lacking the furin sites are not cleaved and have very low activity, channels lacking the furin consensus sites as well as the tract between these sites ([alpha]D206-R231) are active. We analyzed channels with a series of deletions in the tract [alpha]D206-R231 and lacking the [alpha]-subunit furin consensus sites in Xenopus laevis oocytes. We found an eight-residue tract that, when deleted, restored channel activity to the level found in oocytes expressing wild-type ENaC. A synthetic peptide, LPHPLQRL, representing the tract [alpha]L211-L218, inhibited wild-type ENaC expressed in oocytes with an [IC.sub.50] of 0.9 [micro]M, and inhibited channels expressed in collecting duct cells and human primary airway epithelial cells with an [IC.sub.50]s of between ~50 and 100 [micro]M. Analyses of peptides with deletions within this inhibitory tract indicate that eight residues is the minimal backbone length that is required for ENaC inhibition. Analyses of 8-mer peptides with conserved and nonconserved substitutions suggest that [L.sup.1], [P.sup.2], [H.sup.3], [P.sup.4], and [L.sup.8] are required for inhibitory activity. Our findings suggest that this eight-residue tract is a key conserved inhibitory domain that provides epithelial cells with a reserve of inactive channels that can be activated as required by proteases. peptide inhibitors; proteases; furin

Fourier transform electron paramagnetic resonance (FT-EPR) shows the transient free radicals from photolysis of 4-chlorophenol (4CP). The photolysis of 4CP and 4-diazo-2,5-cyclohexadienone give the same FT-EPR spectrum. Thus, a triplet state carbene may result from photoexcitation of 4CP in aqueous and alcohol solutions, which has been previously suggested.

Metal cage complexes [(MeN)MO] (M = Nb, 3; Ta, 4) have been prepared from the reactions of M(NMe) (M = Nb, 1; Ta, 2) with water. Single crystal X-ray diffraction studies of 3 and 4 reveal that they adopt cubane-like structures with M–O bridges. Variable-temperature NMR studies of –NMeMe rotations in 3 and 4 have been performed to give the following activation parameters for the exchanges: Δ H = −1.4(1.1) kJ/mol, Δ S = −209(8) J/mol K, $$ \Updelta G_{{_{{ 30 8\;{\text{K}}}} }}^{{^{ \ne } }} = 6 4\left( 2\right)\;{\text{kJ}}/{\text{mol}} $$ for 3, and Δ H = −0.9(1.2) kJ/mol, Δ S = −2.1(0.2) × 10 J/mol K, $$ \Updelta G_{{ 30 8\;{\text{K}}}}^{{^{ \ne } }} = 6 3\left( 6\right)\;{\text{kJ}}/{\text{mol}} $$ for 4. [ABSTRACT FROM AUTHOR]

Epithelial sodium channels (ENaC) are processed by proteases as they transit the biosynthetic pathway. We recently observed that furin-dependent processing of the α-subunit of ENaC at two sites within its extracellular domain is required for channel activation due to release of a 26-residue inhibitory domain. While channels with α-subunits lacking the furin sites are not cleaved and have very low activity, channels lacking the furin consensus sites as well as the tract between these sites (αD206 -R23 1) are active. We analyzed channels with a series of deletions in the tract αD206-R231 and lacking the α-subunit furin consensus sites in Xenopus laevis oocytes. We found an eight-residue tract that, when deleted, restored channel activity to the level found in oocytes expressing wild-type ENaC. A synthetic peptide, LPHPLQRL, representing the tract αL211-L218, inhibited wild-type ENaC expressed in oocytes with an IC50 of 0.9 μ.M, and inhibited channels expressed in collecting duct cells and human primary airway epithelial cells with an IC50s of between ∼50 and 100 μM. Analyses of peptides with deletions within this inhibitory tract indicate that eight residues is the minimal backbone length that is required for ENaC inhibition. Analyses of 8-mer peptides with conserved and nonconserved substitutions suggest that L¹, P², H³, P4, and L8 are required for inhibitory activity. Our findings suggest that this eight-residue tract is a key conserved inhibitory domain that provides epithelial cells with a reserve of inactive channels that can be activated as required by proteases. [ABSTRACT FROM AUTHOR]

A new trinuclear species containing a Ta(iv)–Ta(iv) bond, Ta3(μ-H)(μ-NMe2)(μNBut)2(NBut)(NMe2)5, has been formed by reductive elimination of H2. Ta2H2(μ-NMe2)2(NMe2)2(NBut)2has also been isolated. O2oxidizes the Ta(iv)–Ta(iv) bond to yield Ta3(μ3-O)(H)(μNBut)(μ-NMe2)2(NMe2)4(NBut)2under ligand exchange. Delocalization of d electrons is discussed. [ABSTRACT FROM AUTHOR]

Presents a study using Fourier transform electron paramagnetic resonance to identify the transient free radicals formed in the photolysis of 4-chlorophenol dissolved in alcohols and to get information on their precursor from CIDEP effects.

Stabilizing cubic polymorph of Li 7 La 3 Zr 2 O 12 at low temperatures is challenging and currently limited to mono- or dual-ion doping with aliovalent ions. Herein, a high-entropy strategy at the Zr sites was deployed to stabilize the cubic phase and lower the lithium diffusion activation energy, evident from the static 7 Li and MAS 6 Li NMR spectra., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Metallacyclic complex [(Me2N)3Ta(η(2)-CH2SiMe2NSiMe3)] (3) undergoes C-H activation in its reaction with H3SiPh to afford a Ta/μ-alkylidene/hydride complex, [(Me2N)2{(Me3Si)2N}Ta(μ-H)2(μ-C-η(2)-CHSiMe2NSiMe3)Ta(NMe2)2] (4). Deuterium-labeling studies with [D3]SiPh show H-D exchange between the Ta-D-Ta unit and all methyl groups in [(Me2N)2{(Me3Si)2N}Ta(μ-D)2(μ-C-η(2)-CHSiMe2NSiMe3)Ta(NMe2)2] ([D2]-4) to give the partially deuterated complex [Dn]-4. In addition, 4 undergoes β-H abstraction between a hydride and an NMe2 ligand and forms a new complex [(Me2N){(Me3 Si)2N}Ta(μ-H)(μ-N-η(2)-C,N-CH2NMe)(μ-C-η(2)-C,N-CHSiMe2NSiMe3)Ta(NMe2)2] (5) with a cyclometalated, η(2)-imine ligand. These results indicate that there are two simultaneous processes in [Dn]-4:1) H-D exchange through σ-bond metathesis, and 2) H-D elimination through β-H abstraction (to give [Dn]-5). Both 4 and 5 have been characterized by single-crystal X-ray diffraction studies., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)