To yield potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with favorable drug-like properties, a series of novel diarylpyrimidine derivatives targeting the tolerant region I NNRTI binding pocket were designed, synthesized and biologically evaluated. The most active inhibitor 10c exhibited outstanding antiviral activity against viral panel, being about 2-fold (wild-type, EC5...

A covalent serine protease inhibitor—Na-p-Tosyl-Lysyl Chloromethylketone (TCK) is a modified lysine residue tosylated at the N-terminus and chloromethylated C-terminus, one molecule of which capable forming two bonds with both Ser His catalytic residues, was co-crystallized oligopeptidase B (OpB) from Serratia proteomaculans (PSPmod). The kinetics study, preceded crystallization, shows that sto...

The pressure sensitivities of the near infrared spectra of the light-harvesting (LH2) complex and a mutant complex with a simplified BChl-B850 binding pocket were compared. In the mutant an abrupt change in the spectral properties occurred at 250 MPa, which was not observed with the native sample. Increased disorder due to collapse of the chromophore pocket is suggested.

Photoreceptor cGMP phosphodiesterases (PDE6 family) are modular enzymes with each catalytic subunit containing two N-terminal regulatory GAF domains, GAF A and GAF B. The GAF A domains contribute to dimerization of the PDE6 catalytic subunits and to binding of the inhibitory Pgamma subunits, and represent candidate sites for noncatalytic binding of cGMP. We performed a mutational analysis of se...