Biomedical subjects

Arnon Chait

Publications and source records attributed to Arnon Chait.

3 recordsLinked to original sources

PubMed2003

Relative hydrophobicity and lipophilicity of drugs measured by aqueous two-phase partitioning, octanol-buffer partitioning and HPLC. A simple model for predicting blood-brain distribution.

Relative hydrophobicity and lipophilicity of 63 compounds with known permeability through the blood-brain barrier (BBB) was examined by partitioning in aqueous dextran-poly(ethylene glycol) two-phase system and octanol-buffer system, and by gradient RP-HPLC at pH 7.4. Combination of the relative hydrophobicity estimates, N(CH(2)) obtained by aqueous two-phase partitioning and the lipophilicity (logD(exp) or logD(HPLC)) values obtained by the shake-flask technique or HPLC technique allows one to differentiate between compounds capable of crossing the BBB and those that cannot. A simple model for predicting blood-brain distribution is proposed.

Blood-Brain Barrier↗

PubMed2003

Efficient protein crystallization.

High-throughput molecular biology and crystallography advances have placed an increasing demand on crystallization, the one remaining bottleneck in macromolecular crystallography. This paper describes three experimental approaches, an incomplete factorial crystallization screen, a high-throughput nanoliter crystallization system, and the use of a neural net to predict crystallization conditions via a small sample (approximately 0.1%) of screening results. The use of these technologies has the potential to reduce time and sample requirements. Initial experimental results indicate that the incomplete factorial design detects initial crystallization conditions not previously discovered using commercial screens. This may be due to the ability of the incomplete factorial screen to sample a broader portion of "crystallization space," using a multidimensional set of components, concentrations, and physical conditions. The incomplete factorial screen is complemented by a neural network program used to model crystallization. This capability is used to help predict new crystallization conditions. An automated, nanoliter crystallization system, with a throughput of up to 400 conditions/h in 40-nl droplets (total volume), accommodates microbatch or traditional "sitting-drop" vapor diffusion experiments. The goal of this research is to develop a fully-automated high-throughput crystallization system that integrates incomplete factorial screen and neural net capabilities.

Computer Simulation↗

PubMed2002

Relative hydrophobicity and lipophilicity of beta-blockers and related compounds as measured by aqueous two-phase partitioning, octanol-buffer partitioning, and HPLC.

Partitioning of 15 beta-blockers and structurally related compounds was examined in aqueous dextran-PEG two-phase systems and octanol-buffer systems at pH from 2.0 up to 12.5. The same compounds were examined by gradient RP-HPLC at pH 2.0, 7.4, and 11.0. The differences between the hydrophobic character of the phases in all three systems at different pH values were characterized using a homologous series of dinitrophenyl-amino acids by measuring the free energy of transfer of a methylene group. Estimates of the relative hydrophobicity, N(CH(2)), and lipophilicity, logD, of the compounds obtained by the three techniques employed were compared. The data indicate that while similar pH profiles for a given compound were established by all these techniques, the information provided is different. It is suggested that the combination of the two descriptors, logD and N(CH(2)), may be useful for quantitative structure-activity relationship analysis of the biological activities involving distribution and/or transport of chemical compounds in biological systems.

Adrenergic beta-Antagonists↗