Abstract:
Glutathionylspermidine synthetase/amidase (GspS) is an essential enzyme in the biosynthesis and turnover of trypanothione and represents an attractive target for the design of selective anti-parasitic drugs. We synthesised a series of analogues of glutathione (L-γ-Glu-L-Leu-Gly-X) where the glycine carboxylic acid group (X) has been substituted for other acidic groups such as tetrazole, hydroxamic acid, acylsulphonamide and boronic acid. The boronic acid appears the most promising lead compound (IC50 of 17.2 μM). © 2002 Elsevier Science Ltd. All rights reserved.
Registro:
Documento: |
Artículo
|
Título: | Glutathione-like tripeptides as inhibitors of glutathionylspermidine synthetase. Part 1: Substitution of the glycine carboxylic acid group |
Autor: | Amssoms, K.; Oza, S.L.; Ravaschino, E.; Yamani, A.; Lambeir, A.-M.; Rajan, P.; Bal, G.; Rodriguez, J.B.; Fairlamb, A.H.; Augustyns, K.; Haemers, A. |
Filiación: | Department of Medicinal Chemistry, University of Antwerp (UIA), Belgium Department of Biochemistry, University of Dundee, Scotland, United Kingdom Departamanto de Quimica Organica, FCEyN, Universidad de Buenos Aires, Argentina Department of Medical Biochemistry, University of Antwerp (UIA), Belgium
|
Palabras clave: | acylsulfonamide; amide; boronic acid derivative; carboxylic acid; enzyme inhibitor; glutathione; glutathione derivative; glutathionylspermidine synthethase; glycine; hydroxamic acid; synthetase; tetrazole derivative; tripeptide; unclassified drug; acidity; amino acid substitution; amino acid synthesis; article; IC 50; protein analysis; Amide Synthases; Carboxylic Acids; Enzyme Inhibitors; Glutathione; Glycine; Oligopeptides |
Año: | 2002
|
Volumen: | 12
|
Número: | 18
|
Página de inicio: | 2553
|
Página de fin: | 2556
|
DOI: |
http://dx.doi.org/10.1016/S0960-894X(02)00489-4 |
Título revista: | Bioorganic and Medicinal Chemistry Letters
|
Título revista abreviado: | Bioorg. Med. Chem. Lett.
|
ISSN: | 0960894X
|
CODEN: | BMCLE
|
CAS: | Amide Synthases, EC 6.3.1.-; Carboxylic Acids; Enzyme Inhibitors; Glutathione, 70-18-8; glutathionylspermidine synthetase, EC 6.3.1.8; Glycine, 56-40-6; Oligopeptides
|
Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0960894X_v12_n18_p2553_Amssoms |
Referencias:
- Fairlamb, A.H., Blackburn, P., Ulrich, P., Chait, B.T., Cerami, A., (1985) Science, 227, p. 1485
- Fairlamb, A.H., Cerami, A., (1992) Ann. Rev. Microbiol., 46, p. 695
- Augystyns, K., Amssoms, K., Yamani, A., Rajan, P.K., Haemers, A., (2001) Curr. Pharm. Des., 7, p. 1117
- Smith, K., Nadeau, K., Bradley, M., Walsh, C., Fairlamb, A.H., (1992) Protein Sci., 1, p. 874
- Tetaud, E., Manai, F., Barrett, M.P., Nadeau, K., Walsh, C.T., Fairlamb, A.H., (1998) J. Biol. Chem., 273, p. 19383
- Verbruggen, C., De Craecker, S., Rajan, P.K., Jiao, X.-Y., Borloo, M., Smith, K., Fairlamb, A.H., Haemers, A., (1996) Bioorg. Med. Chem. Lett., 6, p. 253
- Chen, S., Lin, C.H., Kwon, D.S., Walsh, C.T., Coward, J.K., (1997) J. Med. Chem., 40, p. 3842
- Chen, S., Lin, C.H., Walsh, C.T., Coward, J.K., (1997) Bioorg. Med. Chem. Lett., 7, p. 505
- De Craecker, S., Verbruggen, C., Rajan, P.K., Smith, K., Haemers, A., Fairlamb, A.H., (1997) Mol. Biochem. Parasitol., 84, p. 25
- Tilley, J.W., Danko, W., Loveu, K., Wagner, R., Swistok, J., Makofske, R., Michalewski, J., Weatherford, S., (1991) J. Med. Chem., 34, p. 1125
- Martichonok, V., Jones, B., (1997) J. Biorg. Med. Chem., 5, p. 679
- Odake, S., Okayama, T., Obata, M., Morikawa, T., Hattori, S., Hori, H., Nagai, Y., (1990) Chem. Pharm. Bull., 38, p. 1007
- note; note; Oza, S.L., Ariyanayagam, M.R., Fairlamb, A.H., (2002) Biochem. J., 364, p. 679
Citas:
---------- APA ----------
Amssoms, K., Oza, S.L., Ravaschino, E., Yamani, A., Lambeir, A.-M., Rajan, P., Bal, G.,..., Haemers, A.
(2002)
. Glutathione-like tripeptides as inhibitors of glutathionylspermidine synthetase. Part 1: Substitution of the glycine carboxylic acid group. Bioorganic and Medicinal Chemistry Letters, 12(18), 2553-2556.
http://dx.doi.org/10.1016/S0960-894X(02)00489-4---------- CHICAGO ----------
Amssoms, K., Oza, S.L., Ravaschino, E., Yamani, A., Lambeir, A.-M., Rajan, P., et al.
"Glutathione-like tripeptides as inhibitors of glutathionylspermidine synthetase. Part 1: Substitution of the glycine carboxylic acid group"
. Bioorganic and Medicinal Chemistry Letters 12, no. 18
(2002) : 2553-2556.
http://dx.doi.org/10.1016/S0960-894X(02)00489-4---------- MLA ----------
Amssoms, K., Oza, S.L., Ravaschino, E., Yamani, A., Lambeir, A.-M., Rajan, P., et al.
"Glutathione-like tripeptides as inhibitors of glutathionylspermidine synthetase. Part 1: Substitution of the glycine carboxylic acid group"
. Bioorganic and Medicinal Chemistry Letters, vol. 12, no. 18, 2002, pp. 2553-2556.
http://dx.doi.org/10.1016/S0960-894X(02)00489-4---------- VANCOUVER ----------
Amssoms, K., Oza, S.L., Ravaschino, E., Yamani, A., Lambeir, A.-M., Rajan, P., et al. Glutathione-like tripeptides as inhibitors of glutathionylspermidine synthetase. Part 1: Substitution of the glycine carboxylic acid group. Bioorg. Med. Chem. Lett. 2002;12(18):2553-2556.
http://dx.doi.org/10.1016/S0960-894X(02)00489-4