Chemo-enzymatic fluorination of unactivated organic compounds

Nature Chemical Biology. doi:10.1038/nchembio.128

Authors: Andrea Rentmeister, Frances H Arnold & Rudi Fasan

Fluorination has gained an increasingly important role in drug discovery and development. Here we describe a versatile strategy that combines cytochrome P450–catalyzed oxygenation with deoxofluorination to achieve mono- and polyfluorination of nonreactive sites in a variety of organic scaffolds. This procedure was applied for the rapid identification of fluorinated drug derivatives with enhanced membrane permeability.

Peptidase substrates via global peptide profiling

Nature Chemical Biology. doi:10.1038/nchembio.126

Authors: Debarati M Tagore, Whitney M Nolte, John M Neveu, Roberto Rangel, Liliana Guzman-Rojas, Renata Pasqualini, Wadih Arap, William S Lane & Alan Saghatelian

Peptide metabolism is a complex process that involves many proteins working in concert. Mass spectrometry–based global peptide profiling of mice lacking dipeptidyl peptidase 4 (DPP4) identified endogenous DPP4 substrates and revealed an unrecognized pathway during proline peptide catabolism that interlinks aminopeptidase and DPP4 activities. Together, these studies elucidate specific aspects of DPP4-regulated metabolism and, more generally, highlight the utility of global peptide profiling for studying peptide metabolism in vivo.