Geometrical Analysis of Cytochrome c Unfolding

We have developed a geometrical model to study the unfolding of iso-1 cytochrome c. The model draws on the crystallographic data reported for this protein. These data were used to calculate the distance between specific residues in the folded state, and in a sequence of extended states defined by n= 3, 5, 7, 9, 11, 13, and 15 residue units. Exact calculations carried out for each of the 103 residues in the polypeptide chain demonstrate that different regions of the chain have different unfolding histories. Regions where there is a persistence of compact structures can be identified, and this geometrical characterization is fully consistent with analyses of time-resolved fluorescence energy-transfer (TrFET) data using dansyl-derivatized cysteine side-chain probes at positions 39, 50, 66, 85, and 99. Our calculations were carried out assuming that different regions of the polypeptide chain unfold synchronously. To test this assumption, we performed lattice Monte Carlo simulations to study systematically the possible importance of asynchronicity. Our calculations show that small departures from synchronous dynamics can arise if displacements of residues in the main body of the chain are much more sluggish than near-terminal residues.     

In vivo measurement of nitrogen by NAA

Nitrogen in the human body is measured in vivo using prompt neutron capture gamma-rays. The quantity of nitrogen can then be used as measured of protein. Data are presented on three groups of subjects; volunteers of different ages, those with liver ailments, and those on peritoneal dialysis. The data show that the nitrogen measurements given information (in accord with clinical findings) which is not given by indirect methods of estimating lean body mass.     

Surface plasmons and the extreme anomalous skin effect

We have derived a simple formula for the dispersion relation of surface plasmons on metals in the extreme anomalous skin effect region. Comparisons of this theory with the usual local dielectric theory is made for Cu, Ag, Au, Sn, and Pb. The two theories can be more than two orders of magnitude different in their predictions of propagation lengths, depending on the temperature.     

Regioselective esterification of vicinal diols on monosaccharide derivatives via Mitsunobu reactions

We have carried out a series of esterification reactions of secondary alcohols derived from d-glucose, d-mannose, and d-galactose via the Mitsunobu reaction. The benzoylation reaction of vicinal diols derived from monosaccharides under Mitsunobu conditions afforded monobenzoates with retention of stereochemistry only. The regioselectivity of these reactions depends on the stereochemistry of the sugar starting material. The Mitsunobu reactions on these diols may be used for the selective protection of other vicinal secondary hydroxyl groups.     

14N Solid‐State NMR Spectroscopy of Amino Acids

¹⁴N ultra‐wideline solid‐state NMR (SSNMR) spectra were obtained for 16 naturally occurring amino acids and four related derivatives by using the WURST–CPMG (wideband, uniform rate, and smooth truncation Carr–Purcell–Meiboom–Gill) pulse sequence and frequency‐stepped techniques. The ¹⁴N quadrupolar parameters were measured for the sp³ nitrogen moieties (quadrupolar coupling constant, C_Q, values ranged from 0.8 to 1.5 MHz). With the aid of plane‐wave DFT calculations of the ¹⁴N electric‐field gradient tensor parameters and orientations, the moieties were grouped into three categories according to the values of the quadrupolar asymmetry parameter, η_Q: low (≤0.3), intermediate (0.31–0.7), and high (≥0.71). For RNH₃⁺ moieties, greater variation in N?H bond lengths was observed for systems with intermediate η_Q values than for those with low η_Q values (this variation arose from different intermolecular hydrogen‐bonding arrangements). Strategies for increasing the efficiency of ¹⁴N SSNMR spectroscopy experiments were discussed, including the use of sample deuteration, high‐power ¹H decoupling, processing strategies, high magnetic fields, and broadband cross‐polarization (BRAIN‐CP). The temperature‐dependent rotations of the NH₃ groups and their influence on ¹⁴N transverse relaxation rates were examined. Finally, ¹⁴N SSNMR spectroscopy was used to differentiate two polymorphs of l ‐histidine through their quadrupolar parameters and transverse relaxation time constants. The strategies outlined herein permitted the rapid acquisition of directly detected ¹⁴N SSNMR spectra that to date was not matched by other proposed methods.     

Chemical knockout of pantothenate kinase reveals the metabolic and genetic program responsible for hepatic coenzyme A homeostasis

Coenzyme A (CoA) is the major acyl group carrier in intermediary metabolism. Hopantenate (HoPan), a competitive inhibitor of the pantothenate kinases, was used to chemically antagonize CoA biosynthesis. HoPan dramatically reduced liver CoA and mice developed severe hypoglycemia. Insulin was reduced, glucagon and corticosterone were elevated, and fasting accelerated hypoglycemia. Metabolic profiling revealed a large increase in acylcarnitines, illustrating the role of carnitine in buffering acyl groups to maintain the nonesterified CoASH level. HoPan triggered significant changes in hepatic gene expression that substantially increased the thioesterases, which liberate CoASH from acyl-CoA, and increased pyruvate dehydrogenase kinase 1, which prevents the conversion of CoASH to acetyl-CoA. These results identify the metabolic rearrangements that maintain the CoASH pool which is critical to mitochondrial functions, including gluconeogenesis, fatty acid oxidation, and the tricarboxylic acid and urea cycles.     

Hybrid lipid bilayers in nanostructured silicon: a biomimetic mesoporous scaffold for optical detection of cholera toxin

Cholera toxin levels are optically detected by affinity capture within hybrid lipid bilayer membranes formed in the nanostructures of porous silicon photonic crystals.     

A solid-state 55Mn NMR spectroscopy and DFT investigation of manganese pentacarbonyl compounds

Central transition (55)Mn NMR spectra of several solid manganese pentacarbonyls acquired at magnetic field strengths of 11.75, 17.63, and 21.1 T are presented. The variety of distinct powder sample lineshapes obtained demonstrates the sensitivity of solid-state (55)Mn NMR to the local bonding environment, including the presence of crystallographically unique Mn sites, and facilitates the extraction of the Mn chemical shift anisotropies, CSAs, and the nuclear quadrupolar parameters. The compounds investigated include molecules with approximate C(4v) symmetry, LMn(CO)(5)(L = Cl, Br, I, HgMn(CO)(5), CH(3)) and several molecules of lower symmetry (L = PhCH(2), Ph(3-n)Cl(n)Sn (n= 1, 2, 3)). For these compounds, the Mn CSA values range from <100 ppm for Cl(3)SnMn(CO)(5) to 1260 ppm for ClMn(CO)(5). At 21.1 T the (55)Mn NMR lineshapes are appreciably influenced by the Mn CSA despite the presence of significant (55)Mn quadrupolar coupling constants that range from 8.0 MHz for Cl(3)SnMn(CO)(5) to 35.0 MHz for CH(3)Mn(CO)(5). The breadth of the solid-state (55)Mn NMR spectra of the pentacarbonyl halides is dominated by the CSA at all three applied magnetic fields. DFT calculations of the Mn magnetic shielding tensors reproduce the experimental trends and the magnitude of the CSA is qualitatively rationalized using a molecular orbital, MO, interpretation based on Ramsey's theory of magnetic shielding. In addition to the energy differences between symmetry-appropriate occupied and virtual MOs, the d-character of the Mn MOs is important for determining the paramagnetic shielding contribution to the principal components of the magnetic shielding tensor.