Macrocyclic Mechanism-based Inhibitor for Neuraminidases
Macrocyclic Mechanism-based Inhibitor for Neuraminidases
复制标题
基于大环机制的神经氨酸酶抑制剂
DOI：
10.1002/chem.201200859
复制
发表时间：
2013
期刊：
影响因子：
--
通讯作者：
and Shin-Ichiro Nishimura
中科院分区：
文献类型：
--
作者：
Hirokazu Kai;Hiroshi Hinou;Kentaro Naruchi;Takahiko Matsushita;and Shin-Ichiro Nishimura
A macrocyclic mechanism‐based inhibitor for neuraminidases (NAs) bearing a 2‐difluoromethylphenyl aglycone and a linker between the aglycone and C‐9 positions of sialic acid was synthesized and evaluated. The macrocyclic structure was designed to keep the aglycone moiety in the active site of the neuraminidase after cleavage of the glycoside bond. WhenVibrio chorelaeneuraminidase (VCNA) was treated with a similar acyclic derivative in the presence of detergent, the irreversible inhibition property was disabled. In contrast, this macrocyclic compound acted as an irreversible inhibitor for VCNA in the presence of detergent. Inhibition assay for various NAs using this macrocyclic compound revealed that the irreversible inhibition property depends on thekcatof the neuraminidase treated. NAs having smallkcatvalues, such asInfluenzaviruses,Clostridium, Trypanosoma cruzi, andHuman, were also inhibited irreversibly. However,Salmonella typhimuriumNA, which has an extremely highkcat, was not affected irreversibly by the inhibitor. Interestingly, in contrast to commonkcatinhibitors, the irreversibility of inhibition by this macrocyclic compound is inversely proportional to thekcatof the target neuraminidase.
