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A combination of NMR studies and quantum chemical calculations were employed to investigate the structure and energetics of Zr4+ chelates of pNO2Bn‐DOTA. We have demonstrated that two discrete regioisomeric chelates are generated during the complex formation. The nitrobenzyl substituent can adopt either an equatorial corner or side position on the macrocyclic ring. These regioisomers are incapable of interconversion and were isolated by HPLC. The corner isomer is more stable than the side, and the SAP conformer of both regioisomers is energetically more favorable than the corresponding TSAP conformer. [ABSTRACT FROM AUTHOR]

Taxol (paclitaxel, PTX) is an important anticancer drug that owes it unique activity to its ability to bind to tubulin in a stoichiometric ratio and promote its assembly into microtubules. Experimental results from [sup.2.H]{[sup.19.F}] rotational-echo double resonance nuclear magnetic resonance (REDOR NMR) are presented that provide direct confirmation that paclitaxel adopts a T-shaped conformation when it is bound to tubulin.

Research has been conducted on Staphylococcus aureus intact cells harvested during stationary or exponential growth conditions. The study of these cells carried out via the use of cross-polarization magic-angle spinning and rotational-echo double resonance NMR experiments in the presence of vancomycin allows to determine peptidoglycan cross-link concentrations and suggests that vancomycin interrupts the synthesis of peptidoglycans via interference with transglycosylation.

Results demonstrate that the vancomycin analogue LY329332 binds to peptidoglycan of Staphylococcus aureus in a monomeric form as determined by the rotational-echo double resonance magic angle spinning nuclear magnetic resonance spectoscopy. Characterization of the in situ structure of the antibiotic binding site in the cell wall peptidoglycan is presented.

Chain packing in homogeneous blends of carbonate 13C-labeled bisphenol A polycarbonate with either (i) CF3-labeled bisphenol A polycarbonate or (ii) ring-F-labeled bisphenol A polycarbonate has been characterized using 13C{19F} rotational-echo double-resonance (REDOR) nuclear magnetic resonance. In both blends, the 13C observed spin was at high concentration, and the 19F dephasing or probe spin was at low concentration. In this situation, an analysis in terms of a distribution of isolated heteronuclear pairs of spins is valid. Nearest-neighbor separation of 13C and 19F labels was determined by accurately mapping the initial dipolar evolution using a shifted-pulse version of REDOR. Based on the results of this experiment, the average distance from a ring-fluorine to the nearest 13C==O is more than 1.2 Å greater than the corresponding CF3[Single_Bond]13C==O distance. Next-nearest and more-distant-neighbor separations of labels were measured in a 416-rotor-cycle constant-time version of REDOR for both blends. Statistically significant local order was established for the nearest-neighbor labels in the methyl-labeled blend. These interchain packing results are in qualitative agreement with predictions based on coarse-grained simulations of a specially adapted model for bisphenol A polycarbonate. The model itself has been previously used to determine static and dynamic properties of polycarbonate with results in good agreement with those from rheological and neutron scattering experiments. [ABSTRACT FROM AUTHOR]

The [super 15]N {[super 31]P} REDOR NMR spectra of three metabolically stable phosphonate reaction intermediate analogues complexed to Saccharomyces cerevisiae lumazine synthase are obtained at 7 and 12 T. The resulting models have shown mobility of the Lys92 side chain, which has facilitated the exchange of inorganic phosphate eliminated from the substrate in one reaction, with the organic phosphate-containing substrate needed for the next reaction.

The lipopolysaccharide (LPS) of Vibrio cholerae O139, strain CIRS245, was isolated conventionally, and the lipid A was removed by mild acid hydrolysis (0.1 m NaOAc buffer containing 1 % SDS, pH 4.2, 95 °C, 8 h). The crude product was a complex mixture consisting mainly of constituent fragments of the O‐specific polysaccharide‐core (OSPc). The OSPc was only a minor component in the mixture. Two‐stage purification of the crude OSPc by HPLC gave pure OSPc fragment of the LPS, as shown by NMR spectroscopy, analytical HPLC and ESI‐MS. This material is the purest OSPc fragment of the LPS from Vibrio cholerae O139 reported to date. The purified OSPc was readily converted to the corresponding methyl squarate derivative and the latter was conjugated to BSA. The conjugate, when examined by ELISA, showed immunoreactivity with sera from patients in Bangladesh recovering from cholera caused by V. cholerae O139, but not O1. [ABSTRACT FROM AUTHOR]

We have used C{F}, N{F}, and N{P} rotational-echo double resonance NMR to determine the location and conformation of 19F and 15N double-labeled plusbacin A3 and of double-labeled deslipo-plusbacin A3, each bound to the cell walls of whole cells of Staphyloccocus aureus grown in media containing [1-13C]glycine. The 31P is primarily in wall teichoic acid. Approximately 25% of plusbacin headgroups (the cyclic depsipeptide backbone) are in a closed conformation (N-F separation of 6 Å), while 75% are in a more open conformation (N-F separation of 12 Å). The closed headgroups have no contact with wall teichoic acid, whereas the open headgroups have a strong contact. This places the closed headgroups in hydrophobic regions of the cell wall and the open headgroups in hydrophilic regions. None of the plusbacin tails have contact with the 31P of either wall teichoic acid or the cell membrane and thus are in hydrophobic regions of the cell wall. In addition, both heads and tails of plusbacin A3 have contact with the glycyl 13C incorporated in cell-wall peptidoglycan pentaglycyl bridges and with 13C-labeled purines near the membrane surface. We interpret these results in terms of a dual mode of action for plusbacin A3: first, disruption of the peptidoglycan layer nearest to the membrane surface by closed-conformation plusbacin A3 leading to an inhibition of chain extension by transglycosylation; second, thinning and disruption of the membrane (possibly including disruption of ATP-binding cassette transporters embedded in the membrane) by open-conformation plusbacin A3, thereby leading to release of ATP to the hydrophilic regions of the cell wall and subsequent binding by plusbacin A3. [ABSTRACT FROM AUTHOR]