Dynamic Combinatorial Chemistry to Identify Binders of ThiT, an S-Component of the Energy-Coupling Factor Transporter for Thiamine

作者：Monjas Leticia; Swier Lotteke J Y M; Setyawati Inda; Slotboom Dirk J^*; Hirsch Anna K H^*

来源：ChemMedChem, 2017, 12(20): 1693-1696.

DOI：10.1002/cmdc.201700440

• dynamic combinatorial chemistry
• energy-coupling factor transporter
• flexible protein pockets
• STD NMR spectroscopy
• transmembrane proteins

We applied dynamic combinatorial chemistry (DCC) to identify ligands of ThiT, the S-component of the energy-coupling factor (ECF) transporter for thiamine in Lactococcus lactis. We used a pre-equilibrated dynamic combinatorial library (DCL) and saturation-transfer difference (STD) NMR spectroscopy to identify ligands of ThiT. This is the first report in which DCC is used for fragment growing to an ill-defined pocket, and one of the first reports for its application with an integral membrane protein as target.

• 出版日期2017-10-20