Trypanosoma cruzi trans-sialidase as a drug target against Chagas disease (American trypanosomiasis)

被引:1
作者
Miller, Bill R., III [1 ]
Roitberg, Adrian E. [1 ]
机构
[1] Univ Florida, Dept Chem, Quantum Theory Project, Gainesville, FL 32611 USA
关键词
FREE-ENERGY; MOLECULAR-DOCKING; FORCE-FIELD; SUBSTRATE-SPECIFICITY; CATALYTIC MECHANISM; GENETIC ALGORITHM; LACTOSE ANALOGS; POSE PREDICTION; INHIBITORS; DERIVATIVES;
D O I
10.4155/FMC.13.129
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Chagas disease (or American trypanosomiasis) is a deadly tropical disease that affects millions of people worldwide, primarily in rural regions of South America. Trypanosoma cruzi, the parasitic cause of Chagas disease, possesses a membrane-anchored trans-sialidase enzyme that transfers sialic acids from the host cell surface to the parasitic cell surface, allowing T. cruzi to effectively evade the host's immune system. This enzyme has no analogous human counterpart and thus has become an interesting drug target to combat the parasite. Recent computational efforts have improved our knowledge about the enzyme's structure, dynamics and catalyzed reaction. Many compounds have been tested against trans-sialidase activity, but no strong inhibitors have been identified yet. The current lack of drugs for Chagas disease necessitates more R&D into the design and discovery of strong inhibitors of T. cruzi trans-sialidase.
引用
收藏
页码:1889 / 1900
页数:12
相关论文
共 74 条
[1]   Lactose derivatives are inhibitors of Trypanosoma cruzi trans-sialidase activity toward conventional substrates in vitro and in vivo [J].
Agustí, R ;
París, G ;
Ratier, L ;
Frasch, ACC ;
de Lederkremer, RM .
GLYCOBIOLOGY, 2004, 14 (07) :659-670
[2]   Structural insights into the catalytic mechanism of Trypanosoma cruzi trans-sialidase [J].
Amaya, MF ;
Watts, AG ;
Damager, I ;
Wehenkel, A ;
Nguyen, T ;
Buschiazzo, A ;
Paris, G ;
Frasch, AC ;
Withers, SG ;
Alzari, PM .
STRUCTURE, 2004, 12 (05) :775-784
[3]  
Andrews Norma W., 1993, Biological Research, V26, P65
[4]  
[Anonymous], 2021, CHAG DIS AM TRYP
[5]  
[Anonymous], 1999, STRUCTURE MECH PROTE
[6]   Potent inhibitor scaffold against Trypanosoma cruzi trans-sialidase [J].
Arioka, Shingo ;
Sakagami, Masahiro ;
Uematsu, Rie ;
Yamaguchi, Hiroto ;
Togame, Hiroko ;
Takemoto, Hiroshi ;
Hinou, Hiroshi ;
Nishimura, Shin-ichiro .
BIOORGANIC & MEDICINAL CHEMISTRY, 2010, 18 (04) :1633-1640
[7]   Protein-based virtual screening of chemical databases. 1. Evaluation of different docking/scoring combinations [J].
Bissantz, C ;
Folkers, G ;
Rognan, D .
JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (25) :4759-4767
[8]   BIOLOGY OF TRYPANOSOMA-CRUZI [J].
BRENER, Z .
ANNUAL REVIEW OF MICROBIOLOGY, 1973, 27 :347-382
[9]  
Buchini S., 2008, ANGEW CHEM, V120, P2740
[10]   The crystal structure and mode of action of trans-sialidase, a key enzyme in Trypanosoma cruzi pathogenesis [J].
Buschiazzo, A ;
Amaya, MF ;
Cremona, ML ;
Frasch, AC ;
Alzari, PM .
MOLECULAR CELL, 2002, 10 (04) :757-768