Zolli-Juran Michela, Cechetto Jonathan D, Hartlen Rebecca, Daigle Denis M, Brown Eric D
McMaster HTS Lab, Department of Biochemistry, McMaster University, Hamilton, ON, Canada L8N 3Z5.
Bioorg Med Chem Lett. 2003 Aug 4;13(15):2493-6. doi: 10.1016/s0960-894x(03)00480-3.
This communication describes the high-throughput screen of a diverse library of 50,000 small molecules against Escherichia coli dihydrofolate reductase to detect inhibitors. Sixty-two compounds were identified as having significant inhibitory activity against the enzyme. Secondary screening of these revealed twelve molecules that were competitive with dihydrofolate, nine of which have not been previously characterized as inhibitors of dihydrofolate reductase. These novel molecules ranged in potency (K(i)) from 26 nM to 11 microM and may represent fresh starting points for new small molecule therapeutics directed against dihydrofolate reductase.
本通讯描述了针对大肠杆菌二氢叶酸还原酶对一个包含50,000个小分子的多样文库进行的高通量筛选以检测抑制剂。62种化合物被鉴定为对该酶具有显著抑制活性。对这些化合物的二次筛选揭示了12种与二氢叶酸竞争的分子，其中9种此前未被表征为二氢叶酸还原酶抑制剂。这些新型分子的效力（K(i)）范围为26 nM至11 μM，可能代表针对二氢叶酸还原酶的新型小分子疗法的新起点。
