化学
IC50型
甘露糖苷酶
甘露糖
亚氨基糖
另一个
生物化学
高尔基体
酶
立体化学
体外
内质网
作者
Monika Poláková,Sergej Šesták,Erika Lattová,Ladislav Petruš,Ján Mucha,Igor Tvaroška,Juraj Kóňa
标识
DOI:10.1016/j.ejmech.2011.01.012
摘要
Human Golgi α-mannosidase II (hGM) is a pharmaceutical target for the design of inhibitors with anti-tumor activity. Nanomolar inhibitors of hGM exhibit unwanted co-inhibition of the human lysosomal α-mannosidase (hLM). Hence, improving specificity of the inhibitors directed toward hGM is desired in order to use them in cancer chemotherapy. We report on the rapid synthesis of d-mannose derivatives having one of the RS-, R(SO)- or R(SO2)- groups at the α-anomeric position. Inhibitory properties of thirteen synthesized α-d-mannopyranosides were tested against the recombinant enzyme Drosophila melanogaster homolog of hGM (dGMIIb) and hLM (dLM408). Derivatives with the sulfonyl [R(SO2)-] group exhibited inhibitory activities at the mM level toward both dGMIIb (IC50 = 1.5–2.5 mM) and dLM408 (IC50 = 1.0–2.0 mM). Among synthesized, only the benzylsulfonyl derivative showed selectivity toward dGMIIb. Its inhibitory activity was explained based on structural analysis of the built 3-D complexes of the enzyme with the docked compounds.
科研通智能强力驱动
Strongly Powered by AbleSci AI