Spectroscopic methods to analyze drug metabolites.

Drug metabolites have been monitored with various types of newly developed techniques and/or combination of common analytical methods, which could provide a great deal of information on metabolite profiling. Because it is not easy to analyze whole drug metabolites qualitatively and quantitatively, a single solution of analytical techniques is combined in a multilateral manner to cover the widest range of drug metabolites. Mass-based spectroscopic analysis of drug metabolites has been expanded with the help of other parameter-based methods.

Anti-leukemia activity of a Hsp70 inhibitor and its hybrid molecules.

In this study we examined the anti-leukemia activity of a small molecule inhibitor of Hsp70 proteins, apoptozole (Az), and hybrids in which it is linked to an inhibitor of either Hsp90 (geldanamycin) or Abl kinase (imatinib). The results of NMR studies revealed that Az associates with an ATPase domain of Hsc70 and thus blocks ATP binding to the protein. Observations made in the cell study indicated that Az treatment promotes leukemia cell death by activating caspase-dependent apoptosis without affecting the caspase-independent apoptotic pathway.

Water-Floating Giant Nanosheets from Helical Peptide Pentamers.

One of the important challenges in the development of protein-mimetic materials is understanding the sequence-specific assembly behavior and dynamic folding change. Conventional strategies for constructing two-dimensional (2D) nanostructures from peptides have been limited to using β-sheet forming sequences as building blocks due to their natural tendency to form sheet-like aggregations. We have identified a peptide sequence (YFCFY) that can form dimers via a disulfide bridge, fold into a helix, and assemble into macroscopic flat sheets at the air/water interface.

Screening of Pre-miRNA-155 Binding Peptides for Apoptosis Inducing Activity Using Peptide Microarrays.

MicroRNA-155, one of the most potent miRNAs that suppress apoptosis in human cancer, is overexpressed in numerous cancers, and it displays oncogenic activity. Peptide microarrays, constructed by immobilizing 185 peptides containing the C-terminal hydrazide onto epoxide-derivatized glass slides, were employed to evaluate peptide binding properties of pre-miRNA-155 and to identify its binding peptides. Two peptides, which were identified based on the results of peptide microarray and in vitro Dicer inhibition studies, were found to inhibit generation of mature miRNA-155 catalyzed by Dicer and to enhance expression of miRNA-155 target genes in cells.

Solution structure of Rv0569, potent hypoxic signal transduction protein, from Mycobacterium tuberculosis.

The latent infection is unique characteristic of Mycobacterium tuberculosis to overcome human immune response for its survival. The M. tb develops adaptation to extreme stress conditions to increase the viability, thus easily acquires drug resistance than any other bacteria and maintains a long-term infection status without any symptoms.

Codon optimization enhances protein expression of human peptide deformylase in E. coli.

Human peptide deformylase (hPDF), located in the mitochondria, has recently become a promising target for anti-cancer therapy. However, the expression of the hPDF gene in Escherichia coli is not efficient likely due to extremely high levels of GC content as well as the presence of rare codons. We performed codon optimization of the hPDF gene in order to reduce GC content and to eliminate rare codons.