Discovery of a potent and highly specific β2proteasome inhibitor from a library of copper complexes.
We reported the synthesis, characterization and biological activity of several copper(II) Schiff base complexes, which exhibit high proteasome inhibitory activities with particular selectivity of β2subunit. Structure-activity relationships information obtained from complex Na2[Cu(a4s1)] demonstrated that distinct bonding modes in β2and β5subunits determines its selectivity and potent inhibition for β2subunit.
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
Tongliang
T
Zhou
Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Rare Earth Materials Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Yuanbo
Y
Cai
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: leiliang@bjmu.edu.cn.
Lei
L
Liang
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
Lingfei
L
Yang
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
Fengrong
F
Xu
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
Yan
Y
Niu
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
Chao
C
Wang
Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Rare Earth Materials Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. Electronic address: zhangjl@pku.edu.cn.
Jun-Long
JL
Zhang
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: pingxu@bjmu.edu.cn.
Ping
P
Xu
D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D008958:Models, Molecular; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D012545:Schiff Bases / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D056831:Coordination Complexes; D061988:Proteasome Inhibitors; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D012545:Schiff Bases; D003300:Copper; D046988:Proteasome Endopeptidase Complex
Copper complex; Drug design; Proteasome inhibitors; Schiff base; Structure–activity relationships