Chromatographic separation and NMR characterization of the isomers of MMB-4, a bis-(pyridiniumaldoxime).

1,1'-Methylenebis{4-[(hydroxyimino)methyl]pyridinium) dichloride (MMB-4), a promising antidote for organophosphate poisoning, has been shown by chromatography and NMR to be a mixture of geometric isomers, predominantly the E/E form. The chromatographically separated isomers have been isolated, directly characterized by NMR to be E/E and E/Z isomers of high purity, and shown by HPLC and NMR to re-equilibrate in solution to the isomeric mixture found in bulk MMB-4. These findings clearly show that a minor component in MMB-4 is not an impurity, but a geometric isomer of the principal component and demonstrate the need to understand equilibrium processes for drug characterizations and isomer distributions of chemicals proposed for animal and human clinical trials.

SRP RNA provides the physiologically essential GTPase activation function in cotranslational protein targeting.

The signal recognition particle (SRP) cotranslationally targets proteins to cell membranes by coordinated binding and release of ribosome-associated nascent polypeptides and a membrane-associated SRP receptor. GTP uptake and hydrolysis by the SRP-receptor complex govern this targeting cycle. Because no GTPase-activating proteins (GAPs) are known for the SRP and SRP receptor GTPases, however, it has been unclear whether and how GTP hydrolysis is stimulated during protein trafficking in vivo.

Enhancement of an analytical method for the determination of squalene in anthrax vaccine adsorbed formulations.

Specific lots of anthrax vaccine adsorbed administered to members of the U.S. Armed Forces have been alleged to contain squalene, a chemical purported to be associated with illnesses of Gulf War veterans.

RNA-mediated interaction between the peptide-binding and GTPase domains of the signal recognition particle.

The signal recognition particle (SRP) targets nascent proteins to cellular membranes for insertion or secretion by recognizing polypeptides containing an N-terminal signal sequence as they emerge from the ribosome. GTP-dependent binding of SRP to its receptor protein leads to controlled release of the nascent chain into a membrane-spanning translocon pore. Here we show that the association of the SRP with its receptor triggers a marked conformational change in the complex, localizing the SRP RNA and the adjacent signal peptide-binding site at the SRP-receptor heterodimer interface.

Biodegradation of the hexahydro-1,3,5-trinitro-1,3,5-triazine ring cleavage product 4-nitro-2,4-diazabutanal by Phanerochaete chrysosporium.

Initial denitration of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) by Rhodococcus sp. strain DN22 produces CO2 and the dead-end product 4-nitro-2,4-diazabutanal (NDAB), OHCNHCH2NHNO2, in high yield. Here we describe experiments to determine the biodegradability of NDAB in liquid culture and soils containing Phanerochaete chrysosporium.