Velu Sadanandan E, Mou Liyuan, Luan Chi-Hao, Yang Zhengrong W, DeLucas Lawrence J, Brouillette Christie G, Brouillette Wayne J
Department of Chemistry, Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham, 901 14th Street South, Birmingham, Alabama 35294, USA.
J Med Chem. 2007 May 31;50(11):2612-21. doi: 10.1021/jm061349l. Epub 2007 May 10.
Tethered dimers incorporating natural alpha-amino acid end groups were synthesized, including examples in which the previously reported esterase-sensitive ester linker was replaced with more stable amide or ether linkers. These compounds remained effective both as inhibitors of NAD synthetase and as potent antibacterial agents for Gram-positive strains. Studies on nonspecific effects, including detergent properties and promiscuous inhibition, suggested little contribution to observed activities.
合成了包含天然α-氨基酸端基的束缚二聚体，包括一些实例，其中先前报道的酯酶敏感酯连接体被更稳定的酰胺或醚连接体所取代。这些化合物作为NAD合成酶抑制剂和革兰氏阳性菌株的强效抗菌剂均保持有效。对非特异性作用的研究，包括去污剂性质和混杂抑制，表明其对观察到的活性贡献不大。
