title: Molecular docking of a series of peptidomimetics in the trypanothione binding site of T. cruzi trypanothione reductase.
abstract: Chagas' disease (CD) has been responsible for many deaths and disabilities mainly in South America. Currently, 40 million people are at risk of acquiring this disease and, existing therapies are still unsatisfactory, presenting harsh side effects. Therefore, the development of new chemical entities to reverse this state is critical. A series of peptidomimetics, developed by Mc Kie et al. (2001) [11], showed a reversible and competitive inhibition against Trypanosoma cruzi Trypanothione Reductase (TR). These inhibitors may be used as basis of lead compounds in the design of new drug candidates for the treatment of CD. In this work, we have docked this series of peptidomimetics into the TR binding site, using the FlexX algorithm as implemented in the Sybyl program, in order to access the binding mode of this class of compounds in the target enzyme.
authors.affiliation: Universidade Federal do Rio de Janeiro (UFRJ), Instituto de Química, Laboratório de Modelagem Molecular (LabMMol), Cidade Universitária, Ilha do Fundão, Centro de Tecnologia, Bloco A, 6(o) Andar, Sala 619, Rio de Janeiro, CEP 21941-909, RJ, Brazil. samuelpita@iq.ufrj.br
authors.forename: Samuel Silva
authors.initials: SS
authors.lastname: da Rocha Pita
authors.forename: José Jair Vianna
authors.initials: JJ
authors.lastname: Cirino
authors.forename: Ricardo Bicca
authors.initials: RB
authors.lastname: de Alencastro
authors.forename: Helena Carla
authors.initials: HC
authors.lastname: Castro
authors.forename: Carlos Rangel
authors.initials: CR
authors.lastname: Rodrigues
authors.forename: Magaly Girão
authors.initials: MG
authors.lastname: Albuquerque
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013095:Spermidine / Q000031:analogs & derivatives* / Q000737:chemistry; D014349:Trypanosoma cruzi / Q000201:enzymology*
chemical_list: D010455:Peptides; C044809:trypanothione; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D005978:Glutathione; D013095:Spermidine