coral Software: QSAR for Anticancer Agents.

CORrelations And Logic (coral at http://www.insilico.eu/coral) is freeware aimed at establishing a quantitative structure - property/activity relationships (QSPR/QSAR). Simplified molecular input line entry system (SMILES) is used to represent the molecular structure. In fact, symbols in SMILES nomenclatures are indicators of the presence of defined molecular fragments. By means of the calculation with Monte Carlo optimization of the so called correlation weights (contributions) for the above-mentioned molecular fragments, one can define optimal SMILES-based descriptors, which are correlated with an endpoint for the training set. The predictability of these descriptors for an external validation set can be estimated. A collection of SMILES-based models of anticancer activity of 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridines for different splits into training and validation set which are calculated with the coral are examined and discussed. Good performance has been obtained for three splits: the r(2) ranged between 0.778 and 0.829 for the sub-training set, between 0.828 and 0.933 for the calibration set, and between 0.807 and 0.931 for the validation set.

A new fluorogenic peptide determines proteasome activity in single cells.

The ubiquitin-proteasome system plays a critical role in many diseases, making it an attractive biomarker and therapeutic target. However, the impact of results obtained in vitro using purified proteasome particles or whole cell extracts is limited by the lack of efficient methods to assess proteasome activity in living cells. We have engineered an internally quenched fluorogenic peptide with a proteasome-specific cleavage motif fused to TAT and linked to the fluorophores DABCYL and EDANS. This peptide penetrates cell membranes and is rapidly cleaved by the proteasomal chymotrypsin-like activity, generating a quantitative fluorescent reporter of in vivo proteasome activity as assessed by time-lapse or flow cytometry fluorescence analysis. This reporter is an innovative tool for monitoring proteasomal proteolytic activities in physiological and pathological conditions.