title: Novel bivalent inhibitors with sub-nanomolar affinities towards human glyoxalase I.
abstract: The zinc metalloenzyme glyoxalase I (GlxI) catalyzes the glutathione-dependent inactivation of cytotoxic methylglyoxal. Two competitive bivalent GlxI inhibitors, polyBHG2-62 (Ki=1.0 nM) and polyBHG2-54 (Ki=0.3 nM), were synthesized based on the transition-state analog S-(N-bromophenyl-N-hydroxycarbamoyl) glutathione (BHG). The most effective inhibitor, polyBHG2-54, is the first subnanomolar inhibitor of GlxI, and is over 50-fold more potent than BHG itself.
authors: Department of Antibiotic Research & Re-evaluation, Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Huaguan Road 168, Chengdu City, Sichuan Province 610052, PR China.
authors: Yankui
authors: Y
authors: Sang
authors: Department of Antibiotic Research & Re-evaluation, Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Huaguan Road 168, Chengdu City, Sichuan Province 610052, PR China.
authors: Qing
authors: Q
authors: Shi
authors: Department of Antibiotic Research & Re-evaluation, Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Huaguan Road 168, Chengdu City, Sichuan Province 610052, PR China.
authors: Mingguang
authors: M
authors: Mo
authors: Department of Antibiotic Research & Re-evaluation, Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Huaguan Road 168, Chengdu City, Sichuan Province 610052, PR China.
authors: Caixia
authors: C
authors: Ni
authors: Department of Antibiotic Research & Re-evaluation, Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Huaguan Road 168, Chengdu City, Sichuan Province 610052, PR China.
authors: Zonghe
authors: Z
authors: Li
authors: Department of Antibiotic Research & Re-evaluation, Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Huaguan Road 168, Chengdu City, Sichuan Province 610052, PR China.
authors: Bichong
authors: B
authors: Liu
authors: Department of Antibiotic Research & Re-evaluation, Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Huaguan Road 168, Chengdu City, Sichuan Province 610052, PR China.
authors: Qishan
authors: Q
authors: Deng
authors: Department of Chemistry & Biochemistry, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
authors: Donald J
authors: DJ
authors: Creighton
authors: Department of Antibiotic Research & Re-evaluation, Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Huaguan Road 168, Chengdu City, Sichuan Province 610052, PR China. Electronic address: zhebinzheng@hotmail.com.
authors: Zhe-Bin
authors: ZB
authors: Zheng
mesh_terms: D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; C000597196:GLO1 protein, human; D007791:Lactoylglutathione Lyase
keywords: Bivalent inhibitor; Glyoxalase I; Linker; Methylglyoxal