Literature DB >> 24189737

Rational design of peptide-based inhibitors of trypanothione reductase as potential antitrypanosomal drugs.

J Garforth1, J H McKie, R Jaouhari, T J Benson, A H Fairlamb, K T Douglas.   

Abstract

The rational design of ligands for the substrate-binding site of a homology-modelled trypanothione reductase (TR) was performed. Peptides were designed to be selective for TR over human glutathione reductase (GR). The design process capitalized on the proposed differences between the activesites of TR and human GR, subsequently confirmed by the TR crystal structure. Enzyme kinetics confirmed that forT. cruzi TR benzoyl-Leu-Arg-Arg-ß-naphthylamide was an inhibitor (Ki 13.8µM) linearly competitive with the native substrate, trypanothione disulphide, and did not inhibit glutathione reductase.

Entities:  

Year:  1994        PMID： 24189737     DOI： 10.1007/BF00813749

Source DB:  PubMed          Journal:  Amino Acids        ISSN： 0939-4451            Impact factor:   3.520


  9 in total

1.  Rationally designed selective inhibitors of trypanothione reductase. Phenothiazines and related tricyclics as lead structures.

Authors:  T J Benson; J H McKie; J Garforth; A Borges; A H Fairlamb; K T Douglas
Journal:  Biochem J       Date:  1992-08-15       Impact factor: 3.857

2.  Active site of trypanothione reductase. A target for rational drug design.

Authors:  W N Hunter; S Bailey; J Habash; S J Harrop; J R Helliwell; T Aboagye-Kwarteng; K Smith; A H Fairlamb
Journal:  J Mol Biol       Date:  1992-09-05       Impact factor: 5.469

3.  X-ray structure of trypanothione reductase from Crithidia fasciculata at 2.4-A resolution.

Authors:  J Kuriyan; X P Kong; T S Krishna; R M Sweet; N J Murgolo; H Field; A Cerami; G B Henderson
Journal:  Proc Natl Acad Sci U S A       Date:  1991-10-01       Impact factor: 11.205

Review 4.  Molecular studies on trypanothione reductase, a target for antiparasitic drugs.

Authors:  C Walsh; M Bradley; K Nadeau
Journal:  Trends Biochem Sci       Date:  1991-08       Impact factor: 13.807

5.  Glutathione reductase from human erythrocytes. Isolation of the enzyme and sequence analysis of the redox-active peptide.

Authors:  G Krohne-Ehrich; R H Schirmer; R Untucht-Grau
Journal:  Eur J Biochem       Date:  1977-10-17

6.  Refined structure of glutathione reductase at 1.54 A resolution.

Authors:  P A Karplus; G E Schulz
Journal:  J Mol Biol       Date:  1987-06-05       Impact factor: 5.469

7.  Human glutathione reductase: purification of the crystalline enzyme from erythrocytes.

Authors:  D J Worthington; M A Rosemeyer
Journal:  Eur J Biochem       Date:  1974-10-01

8.  Expression of Trypanosoma congolense trypanothione reductase in Escherichia coli: overproduction, purification, and characterization.

Authors:  F X Sullivan; S L Shames; C T Walsh
Journal:  Biochemistry       Date:  1989-06-13       Impact factor: 3.162

9.  Synthesis of N-benzyloxycarbonyl-L-cysteinylglycine 3-dimethylaminopropylamide disulfide: a cheap and convenient new assay for trypanothione reductase.

Authors:  A el-Waer; K T Douglas; K Smith; A H Fairlamb
Journal:  Anal Biochem       Date:  1991-10       Impact factor: 3.365
  9 in total
  2 in total

1.  Synthesis of symmetric disulfides as potential alternative substrates for trypanothione reductase and glutathione reductase: Part 1.

Authors:  R Jaouhari; T Besheya; J H McKie; K T Douglas
Journal:  Amino Acids       Date:  1995-12       Impact factor: 3.520

2.  Trypanothione reductase: a viable chemotherapeutic target for antitrypanosomal and antileishmanial drug design.

Authors:  M Omar F Khan
Journal:  Drug Target Insights       Date:  2007-06-19
  2 in total

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