Classification scheme for the design of serine protease targeted compound libraries.

The development of a scoring scheme for the classification of molecules into serine protease (SP) actives and inactives is described. The method employed a set of pre-selected descriptors for encoding the molecular structures, and a trained neural network for classifying the molecules. The molecular requirements were profiled and validated by using available databases of SP- and non-SP-active agents [1,439 diverse SP-active molecules, and 5,131 diverse non-SP-active molecules from the Ensemble Database (Prous Science, 2002)] and Sensitivity Analysis.

New diversity calculations algorithms used for compound selection.

Some modifications were introduced into the previously described Centroid diversity sorting algorithm, which uses cosine similarity metric. The modified algorithm is suitable for the work with large databases on personal computers. For example, for diversity sorting of the database with the size greater than a million of records, less than 9 h are required (Pentium III, 800 MHz).

Platelet-activating factor stimulates receptor-mediated formation of reactive oxygen intermediates in human monocytes.

Stimulation of production of reactive oxygen intermediates (ROI) was examined in human peripheral blood monocytes by luminol-dependent chemiluminescence. The dose-response curve characterizing the dependence of ROI production on the concentration of platelet-activating factor (PAF) showed that stimulation occurred within a concentration range of 2 x 10(-9)M to 5 x 10(-6)M. Transformation of the dose-response curve to an Eadie-Hofstee plot indicated that the process is characterized by two Km values.