Small molecule modulation of the human chromatid decatenation checkpoint.

After chromosome replication, the intertwined sister chromatids are disentangled by topoisomerases. The integrity of this process is monitored by the chromatid decatenation checkpoint. Here, we describe small molecule modulators of the human chromatid decatenation checkpoint identified using a cell-based, chemical genetic modifier screen.

Multidimensional chemical genetic analysis of diversity-oriented synthesis-derived deacetylase inhibitors using cell-based assays.

Systematic chemical genetics aims to explore the space representing interactions between small molecules and biological systems. Beyond measuring binding interactions and enzyme inhibition, measuring changes in the activity of proteins in intact signaling networks is necessary. Toward this end, we are partitioning chemical space into regions with different biological activities using a panel of cell-based assays and small molecule "chemical genetic modifiers.

Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation.

Protein acetylation, especially histone acetylation, is the subject of both research and clinical investigation. At least four small-molecule histone deacetylase inhibitors are currently in clinical trials for the treatment of cancer. These and other inhibitors also affect microtubule acetylation.

The chemistry of amine-azide interconversion: catalytic diazotransfer and regioselective azide reduction.

Azides have proven to be useful precursors to amines in organic syntheses. This report describes an improvement of the diazotransfer reaction and the first example of a regioselective azide reduction of compounds containing multiple azides. The use of a specific ratio of solvents and zinc chloride as a catalyst resulted in a more efficient diazotransfer reaction capable of delivering >90% conversion per amine with shorter reaction times than those previously reported.