Inhibitory effects of angiotensin receptor blockers on CYP2C9 activity in human liver microsomes.

We investigated the inhibitory effects of the angiotensin receptor blockers (ARBs), candesartan, irbesartan, losartan, losartan active metabolite (EXP-3174), olmesartan, telmisartan and valsartan (0.3-300 microM), on the CYP2C9 activity in human liver microsomes using (S)-(-)-warfarin as a typical CYP2C9 substrate. Except for olmesartan and valsartan, these ARBs inhibited the activity of 7-hydroxylation of (S)-(-)-warfarin with IC50 values of 39.

SNP genotyping by allele-specific PCR using ENA primers.

When we placed a 2'-O,4'-C-ethylene nucleic acid (ENA) residue into primers at the 3' end, or the n-1, n-2 or n-3 position, which included a single nucleotide polymorphism (SNP) site at the 3' end, only primers containing the ENA residue at the n-2 position were read by Taq DNA polymerase for amplification. When we compared n-2-position-modified ENA with the corresponding unmodified DNA primers that are often used for allele-specific PCR (AS-PCR), a greater discrimination of the SNP site by ENA primers was observed. This improvement is probably due to the difficulty of incorporating a nucleotide into a mismatched ENA primer by Taq DNA polymerase in the primer-template duplex.

Structural elucidation of A-74528, an inhibitor for 2',5'-phosphodiesterase isolated from Streptomyces sp.

A-74528 (1) is a metabolite of Streptomyces sp. discovered in the screening for 2',5'-oligoadenylate phosphodiesterase inhibitors. The planar structure of 1 was mainly elucidated by NMR techniques including natural abundance INADEQUATE, and the relative configuration and the conformation were elucidated by the analyses of NOEs and assessment of dihedral angles predicted by QUANTA/CHARMm computations and coupling constants.

Improvement of single nucleotide polymorphism genotyping by allele-specific PCR using primers modified with an ENA residue.

When we placed an ENA residue into primers at the 3' end, or the n-1, n-2, or n-3 position, which included a single nucleotide polymorphism (SNP) site at the 3' end, only primers containing the ENA residue at the n-2 position were read by Taq DNA polymerase for amplification. The use of the ENA primers avoided the generation of undesired short products, which are thought to be derived from primer-dimers. A greater discrimination of the SNP site by these primers containing the ENA residue was observed compared with that of the corresponding unmodified DNA primers that are often used for allele-specific polymerase chain reaction (AS-PCR).

Comparison of enzymatic properties between hPADI2 and hPADI4.

In the sera of rheumatoid arthritis (RA) patients, autoantibodies directed to citrullinated proteins are found with high specificity for RA. Peptidylarginine deiminases (PADIs) are enzymes responsible for protein citrullination. Among many isoforms of PADIs, only PADI4 has been identified as an RA-susceptibility gene.

Binding mode of ecdysone agonists to the receptor: comparative modeling and docking studies.

Three-dimensional structure models of the ligand-binding domain of the ecdysone receptor of Heliothis virescens were built by the homology modeling technique from the crystal structures of nuclear receptors. Two models were created based both on known ligand-binding domain structures of the receptors with the highest sequence identity to the ecdysone receptor, and on those of steroid hormone receptors. The latter model, which was found to have better stereochemical quality and be in good agreement with the binding of the steroidal framework of the endogenous agonist 20-hydroxyecdysone, was used for docking studies.

An efficient method for reconstructing protein backbones from alpha-carbon coordinates.

We present an approach for building protein backbones from alpha-carbon (Calpha) coordinates. The approach is analytical and based on the information of favored regions in the Ramachandran map. The backbone construction consists of three parts: prediction of (phi, psi) angle pairs from the Calpha trace, generation of atomic coordinates with these (phi, psi) angles, and refinement by subsequent energy minimization.