The Experts below are selected from a list of 207 Experts worldwide ranked by ideXlab platform
Kenneth T. Douglas - One of the best experts on this subject based on the ideXlab platform.
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Peptoid inhibition of trypanothione reductase as a potential antitrypanosomal and antileishmanial drug lead.
Amino Acids, 2002Co-Authors: Cecil Chan, Alan H Fairlamb, James H. Mckie, Kenneth T. DouglasAbstract:One route to the design of lead compounds for rational drug design approaches to developing drugs against trypanosomiasis, Chagas' disease and leishmaniasis is to develop novel inhibitors of the parasite-specific enzyme trypanothione reductase. A lead inhibitor based on a peptoid structure was designed in the present study based on the known strong competitive inhibition of trypanothione reductase by N-benzoyl-Leu-Arg-Arg-β-naphthylamide and N-Benzyloxycarbonyl-Ala-Arg-Arg-4-methoxy-β-naphthylamide. In the target peptoid the arginyl residues were replaced by alkylimidazolium units and the Benzyloxycarbonyl Group by the benzylaminocarbonyl function. The peptoid was synthesised using t-butoxycarbonyl protection chemistry and couplings were activated by 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate. The resulting peptoid was shown to be a competitive inhibitor of recombinant trypanothione reductase from Trypanosoma cruzi with a Ki value of 179 μM and with only weak inhibition of human erythrocyte glutathione reductase (the inhibition of glutathione reductase was at least 291-fold weaker than of trypanothione reductase).
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Synthesis and enzymology of modified N-Benzyloxycarbonyl-L-cysteinylglycyl-3,3-dimethylaminopropylamide++ + disulphides as alternative substrates for trypanothione reductase from Trypanosoma cruzi: Part 3.
Amino acids, 1999Co-Authors: C. T. Yuen, Alan H Fairlamb, James H. Mckie, Jacqui Garforth, T. Besheya, Rabih Jaouhari, Kenneth T. DouglasAbstract:Kinetic data for alternative substrates of recombinant trypanothione reductase fromTrypanosoma cruzi were measured for a series ofN-substituted-L-cysteinylglycyl-3-dimethylaminopropylamides, in which the cysteineN-substituent was either a variant of the Benzyloxycarbonyl Group or was L-phenylalanine or L-tryptophan. Replacing the benzylic ether oxygen atom by CH2. or NH had relatively minor effects on kcat, but raised the value of Km, 4.5- and 10-fold, respectively. Similarly, relative to the carbobenzoxy Group, anN-L-phenylalanyl orN-L-tryptophanyl replacement on the cysteine hardly altered kcat, but increased Km, values by 16.6 and 7.4 fold, respectively. These observations were consistent with the Km, values referring primarily to binding for this series of nonspecific substrates.
Alan H Fairlamb - One of the best experts on this subject based on the ideXlab platform.
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Peptoid inhibition of trypanothione reductase as a potential antitrypanosomal and antileishmanial drug lead.
Amino Acids, 2002Co-Authors: Cecil Chan, Alan H Fairlamb, James H. Mckie, Kenneth T. DouglasAbstract:One route to the design of lead compounds for rational drug design approaches to developing drugs against trypanosomiasis, Chagas' disease and leishmaniasis is to develop novel inhibitors of the parasite-specific enzyme trypanothione reductase. A lead inhibitor based on a peptoid structure was designed in the present study based on the known strong competitive inhibition of trypanothione reductase by N-benzoyl-Leu-Arg-Arg-β-naphthylamide and N-Benzyloxycarbonyl-Ala-Arg-Arg-4-methoxy-β-naphthylamide. In the target peptoid the arginyl residues were replaced by alkylimidazolium units and the Benzyloxycarbonyl Group by the benzylaminocarbonyl function. The peptoid was synthesised using t-butoxycarbonyl protection chemistry and couplings were activated by 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate. The resulting peptoid was shown to be a competitive inhibitor of recombinant trypanothione reductase from Trypanosoma cruzi with a Ki value of 179 μM and with only weak inhibition of human erythrocyte glutathione reductase (the inhibition of glutathione reductase was at least 291-fold weaker than of trypanothione reductase).
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Synthesis and enzymology of modifiedN-Benzyloxycarbonyl-L-cysteinylglycyl-3,3-dimethylaminopropylamide disulphides as alternative substrates for trypanothione reductase fromTrypanosoma crud: Part 3
Amino Acids, 1999Co-Authors: C. T. Yuen, Alan H Fairlamb, Jacqui Garforth, T. Besheya, Rabih Jaouhari, J. H. Mckie, K. T. DouglasAbstract:Kinetic data for alternative substrates of recombinant trypanothione reductase from Trypanosoma cruzi were measured for a series of N -substituted-L-cysteinylglycyl-3-dimethylaminopropylamides, in which the cysteine N -substituent was either a variant of the Benzyloxycarbonyl Group or was L-phenylalanine or L-tryptophan. Replacing the benzylic ether oxygen atom by CH_2. or NH had relatively minor effects on k_cat, but raised the value of K_m, 4.5- and 10-fold, respectively. Similarly, relative to the carbobenzoxy Group, an N -L-phenylalanyl or N -L-tryptophanyl replacement on the cysteine hardly altered k_cat, but increased K_m, values by 16.6 and 7.4 fold, respectively. These observations were consistent with the K_m, values referring primarily to binding for this series of nonspecific substrates.
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Synthesis and enzymology of modified N-Benzyloxycarbonyl-L-cysteinylglycyl-3,3-dimethylaminopropylamide++ + disulphides as alternative substrates for trypanothione reductase from Trypanosoma cruzi: Part 3.
Amino acids, 1999Co-Authors: C. T. Yuen, Alan H Fairlamb, James H. Mckie, Jacqui Garforth, T. Besheya, Rabih Jaouhari, Kenneth T. DouglasAbstract:Kinetic data for alternative substrates of recombinant trypanothione reductase fromTrypanosoma cruzi were measured for a series ofN-substituted-L-cysteinylglycyl-3-dimethylaminopropylamides, in which the cysteineN-substituent was either a variant of the Benzyloxycarbonyl Group or was L-phenylalanine or L-tryptophan. Replacing the benzylic ether oxygen atom by CH2. or NH had relatively minor effects on kcat, but raised the value of Km, 4.5- and 10-fold, respectively. Similarly, relative to the carbobenzoxy Group, anN-L-phenylalanyl orN-L-tryptophanyl replacement on the cysteine hardly altered kcat, but increased Km, values by 16.6 and 7.4 fold, respectively. These observations were consistent with the Km, values referring primarily to binding for this series of nonspecific substrates.
C. T. Yuen - One of the best experts on this subject based on the ideXlab platform.
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Synthesis and enzymology of modifiedN-Benzyloxycarbonyl-L-cysteinylglycyl-3,3-dimethylaminopropylamide disulphides as alternative substrates for trypanothione reductase fromTrypanosoma crud: Part 3
Amino Acids, 1999Co-Authors: C. T. Yuen, Alan H Fairlamb, Jacqui Garforth, T. Besheya, Rabih Jaouhari, J. H. Mckie, K. T. DouglasAbstract:Kinetic data for alternative substrates of recombinant trypanothione reductase from Trypanosoma cruzi were measured for a series of N -substituted-L-cysteinylglycyl-3-dimethylaminopropylamides, in which the cysteine N -substituent was either a variant of the Benzyloxycarbonyl Group or was L-phenylalanine or L-tryptophan. Replacing the benzylic ether oxygen atom by CH_2. or NH had relatively minor effects on k_cat, but raised the value of K_m, 4.5- and 10-fold, respectively. Similarly, relative to the carbobenzoxy Group, an N -L-phenylalanyl or N -L-tryptophanyl replacement on the cysteine hardly altered k_cat, but increased K_m, values by 16.6 and 7.4 fold, respectively. These observations were consistent with the K_m, values referring primarily to binding for this series of nonspecific substrates.
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Synthesis and enzymology of modified N-Benzyloxycarbonyl-L-cysteinylglycyl-3,3-dimethylaminopropylamide++ + disulphides as alternative substrates for trypanothione reductase from Trypanosoma cruzi: Part 3.
Amino acids, 1999Co-Authors: C. T. Yuen, Alan H Fairlamb, James H. Mckie, Jacqui Garforth, T. Besheya, Rabih Jaouhari, Kenneth T. DouglasAbstract:Kinetic data for alternative substrates of recombinant trypanothione reductase fromTrypanosoma cruzi were measured for a series ofN-substituted-L-cysteinylglycyl-3-dimethylaminopropylamides, in which the cysteineN-substituent was either a variant of the Benzyloxycarbonyl Group or was L-phenylalanine or L-tryptophan. Replacing the benzylic ether oxygen atom by CH2. or NH had relatively minor effects on kcat, but raised the value of Km, 4.5- and 10-fold, respectively. Similarly, relative to the carbobenzoxy Group, anN-L-phenylalanyl orN-L-tryptophanyl replacement on the cysteine hardly altered kcat, but increased Km, values by 16.6 and 7.4 fold, respectively. These observations were consistent with the Km, values referring primarily to binding for this series of nonspecific substrates.
Jean-louis Montero - One of the best experts on this subject based on the ideXlab platform.
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Influence of the Benzyloxycarbonyl Protective Group on Glycosylation with Mannopyranosyl Donors
Journal of Carbohydrate Chemistry, 2006Co-Authors: Alain Morère, Fouzi Mouffouk, Simon Leiris, Alain Leydet, Jean-louis MonteroAbstract:The perBenzyloxycarbonylation of D‐mannose, D‐glucose, and D‐galactose was achieved in high yield. In the mannose series, the selective removal of the anomeric Benzyloxycarbonyl Group followed by the activation of the anomeric position furnished, depending on the activation conditions, either a bromo glycosyl donor or a trichloroacetimidate donor. The trichloroacetimidate donor, protected by Benzyloxycarbonyl Groups, was used successfully for the synthesis of a disaccharide.
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The Benzyloxycarbonyl Group: An alternative protective Group in the mannose series
Carbohydrate Research, 1997Co-Authors: Alain Morère, Chantal Menut, Carole Vidil, Philip Skaanderup, Jesper Thorsen, Jean-pierre Roque, Jean-louis MonteroAbstract:Abstract A procedure for the O-Benzyloxycarbonylation at positions 2–4 in the mannose series is described. Starting from methyl 6-O-( 4-methoxy)trityl-α- d -mannopyranoside, methyl 2,3,4-tri -O- Benzyloxycarbonyl-6 -O- (4-methoxy)trityl-α- d -mannopyranoside was obtained.
James H. Mckie - One of the best experts on this subject based on the ideXlab platform.
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Peptoid inhibition of trypanothione reductase as a potential antitrypanosomal and antileishmanial drug lead.
Amino Acids, 2002Co-Authors: Cecil Chan, Alan H Fairlamb, James H. Mckie, Kenneth T. DouglasAbstract:One route to the design of lead compounds for rational drug design approaches to developing drugs against trypanosomiasis, Chagas' disease and leishmaniasis is to develop novel inhibitors of the parasite-specific enzyme trypanothione reductase. A lead inhibitor based on a peptoid structure was designed in the present study based on the known strong competitive inhibition of trypanothione reductase by N-benzoyl-Leu-Arg-Arg-β-naphthylamide and N-Benzyloxycarbonyl-Ala-Arg-Arg-4-methoxy-β-naphthylamide. In the target peptoid the arginyl residues were replaced by alkylimidazolium units and the Benzyloxycarbonyl Group by the benzylaminocarbonyl function. The peptoid was synthesised using t-butoxycarbonyl protection chemistry and couplings were activated by 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate. The resulting peptoid was shown to be a competitive inhibitor of recombinant trypanothione reductase from Trypanosoma cruzi with a Ki value of 179 μM and with only weak inhibition of human erythrocyte glutathione reductase (the inhibition of glutathione reductase was at least 291-fold weaker than of trypanothione reductase).
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Synthesis and enzymology of modified N-Benzyloxycarbonyl-L-cysteinylglycyl-3,3-dimethylaminopropylamide++ + disulphides as alternative substrates for trypanothione reductase from Trypanosoma cruzi: Part 3.
Amino acids, 1999Co-Authors: C. T. Yuen, Alan H Fairlamb, James H. Mckie, Jacqui Garforth, T. Besheya, Rabih Jaouhari, Kenneth T. DouglasAbstract:Kinetic data for alternative substrates of recombinant trypanothione reductase fromTrypanosoma cruzi were measured for a series ofN-substituted-L-cysteinylglycyl-3-dimethylaminopropylamides, in which the cysteineN-substituent was either a variant of the Benzyloxycarbonyl Group or was L-phenylalanine or L-tryptophan. Replacing the benzylic ether oxygen atom by CH2. or NH had relatively minor effects on kcat, but raised the value of Km, 4.5- and 10-fold, respectively. Similarly, relative to the carbobenzoxy Group, anN-L-phenylalanyl orN-L-tryptophanyl replacement on the cysteine hardly altered kcat, but increased Km, values by 16.6 and 7.4 fold, respectively. These observations were consistent with the Km, values referring primarily to binding for this series of nonspecific substrates.