Cardellina John H, Vieira Rebecca C, Eccard Vanessa, Skerry Janet, Montgomery Vicki, Campbell Yvette, Roxas-Duncan Virginia, Leister William, Leclair Christopher A, Maloney David J, Padula Daniele, Pescitelli Gennaro, Khavrutskii Ilja, Hu Xin, Wallqvist Anders, Smith Leonard A
Division of Integrated Toxicology, U.S. Army Medical Research Institute for Infectious Diseases, Frederick, MD.
ACS Med Chem Lett. 2011 Mar 10;2(5):396-401. doi: 10.1021/ml200028z.
The racemic product of the Betti reaction of 5-chloro-8-hydroxyquinoline, benzaldehyde and 2-aminopyridine was separated by chiral HPLC to determine which enantiomer inhibited botulinum neurotoxin serotype A. When the enantiomers unexpectedly proved to have comparable activity, the absolute structures of (+)-(R)-1 and (-)-(S)-1 were determined by comparison of calculated and observed circular dichroism spectra. Molecular modeling studies were undertaken in an effort to understand the observed bioactivity and revealed different ensembles of binding modes, with roughly equal binding energies, for the two enantiomers.
通过手性高效液相色谱法分离了5-氯-8-羟基喹啉、苯甲醛和2-氨基吡啶的贝蒂反应的外消旋产物，以确定哪种对映体抑制A型肉毒杆菌神经毒素。当意外地证明对映体具有相当的活性时，通过比较计算的和观察到的圆二色光谱确定了(+)-(R)-1和(-)-(S)-1的绝对结构。进行了分子模拟研究，以试图理解观察到的生物活性，并揭示了两种对映体具有大致相等结合能的不同结合模式组合。
