Biomedical subjects

Richard Beger

Publications and source records attributed to Richard Beger.

3 recordsLinked to original sources

PubMed2004

Building an organ-specific carcinogenic database for SAR analyses.

FDA reviewers need a means to rapidly predict organ-specific carcinogenicity to aid in evaluating new chemicals submitted for approval. This research addressed the building of a database to use in developing a predictive model for such an application based on structure-activity relationships (SAR). The Internet availability of the Carcinogenic Potency Database (CPDB) provided a solid foundation on which to base such a model. The addition of molecular structures to the CPDB provided the extra ingredient necessary for SAR analyses. However, the CPDB had to be compressed from a multirecord to a single record per chemical database; multiple records representing each gender, species, route of administration, and organ-specific toxicity had to be summarized into a single record for each study. Multiple studies on a single chemical had to be further reduced based on a hierarchical scheme. Structural cleanup involved removal of all chemicals that would impede the accurate generation of SAR type descriptors from commercial software programs; that is, inorganic chemicals, mixtures, and organometallics were removed. Counterions such as Na, K, sulfates, hydrates, and salts were also removed for structural consistency. Structural modification sometimes resulted in duplicate records that also had to be reduced to a single record based on the hierarchical scheme. The modified database containing 999 chemicals was evaluated for liver-specific carcinogenicity using a variety of analysis techniques. These preliminary analyses all yielded approximately the same results with an overall predictability of about 63%, which was comprised of a sensitivity of about 30% and a specificity of about 77%.

Animals↗

PubMed2004

A kinetic study on the degradation of erythromycin A in aqueous solution.

The pH is a critical factor determining the rate of the degradation of erythromycin A in aqueous solutions. However, the kinetics of the acid- and base-catalyzed degradation is still uncertain. This study used a sensitive coulometric detection method to determine concentrations of erythromycin A and its degradation products. To determine the buffer-independent rate constants, sodium acetate (0.05-0.2 M) and Tris-HCl (0.1-0.5 M) were used in a pH range of 3.5-5.5 and 7.0-9.0, respectively. In acidic conditions, anhydroerythromycin A appeared to be produced directly through an internal dehydration of erythromycin A-6,9-hemiketal which simultaneously established an equilibrium with erythromycin A enol ether on the other hand. In weakly alkaline conditions, hydroxide ion appeared to catalyze the hydrolysis of the lactonyl ester bond of erythromycin A-6,9-hemiketal by the pseudo-first-order kinetics, and the C13 --> C11 translactonization and internal dehydration reactions subsequently occurred to form pseudoerythromycin A enol ether. We suggest here a predictive model for reasonable interpretation of the kinetics of erythromycin A degradation in aqueous solutions, in which the observed rate constant was expressed by the sum of the partial reaction rate constants for the acid- and base-catalyzed degradation of erythromycin A-6,9-hemiketal as a function of pH in a range of 3.0-10.0.

Anti-Bacterial Agents↗

PubMed2003

Assessment of the molecular dynamics structure of DNA in solution based on calculated and observed NMR NOESY volumes and dihedral angles from scalar coupling constants.

To assess the accuracy of the molecular dynamics (MD) models of nucleic acids, a detailed comparison between MD-calculated and NMR-observed indices of the dynamical structure of DNA in solution has been carried out. The specific focus of our comparison is the oligonucleotide duplex, d(CGCGAATTCGCG)(2), for which considerable structural data have been obtained from crystallography and NMR spectroscopy. An MD model for the structure of d(CGCGAATTCGCG)(2) in solution, based on the AMBER force field, has been extended with a 14 ns trajectory. New NMR data for this sequence have been obtained in order to allow a detailed and critical comparison between the calculated and observed parameters. Observable two-dimensional (2D) nuclear Overhauser effect spectroscopy (NOESY) volumes and scalar coupling constants were back-calculated from the MD trajectory and compared with the corresponding NMR data. The comparison of these results indicate that the MD model is in generally good agreement with the NMR data, and shows closer accord with experiment than back-calculations based on the crystal structure of d(CGCGAATTCGCG)(2) or the canonical A or B forms of the sequence. The NMR parameters are not particularly sensitive to the known deficiency in the AMBER MD model, which is a tendency toward undertwisting of the double helix when the parm.94 force field is used. The MD results are also compared with a new determination of the solution structure of d(CGCGAATTCGCG)(2) using NMR dipolar coupling data.

Base Sequence↗