Abstract
Hydrophobic amino acid esters and peptides disrupt lysosomes in cell-free fractions by a mechanism involving trapping by protonation, enzymatic hydrolysis and accumulation of less permeant products within the organelles (Goldman & Naider 1974; Ransom & Reeves 1983). Damage to lysosomes possibly accounts for the selective toxicity of the compounds for monocytes, NK cells and cytotoxic T cells. This toxicity may be due to ester conversion to membranolytic polymers catalysed by a dipeptidyl-peptidase I (Thiele & Lipsky 1990 a, b).
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References
Alfieri SC, Zilberfarb V, Rabinovitch M (1987) Destruction of Leishmania mexicana amazonensis amastigotes by leucine methyl ester: protection by other amino acid esters. Parasitology 95:31–41
Alfieri SC, Ramazeilles C, Zilberfarb V, Galpin I J, Norman SE, Rabinovitch M (1988). Proteinase inhibitors protect Leishmania amazonensis amastigotes from destruction by amino acid esters. Mol Biochem Parasitol 29:191–201
Alfieri SC, Shaw E, Zilberfarb V, Rabinovitch M (1989) Leishmania amazonensis: involvement of cysteine proteinases in the killing of isolated amastigotes by L- Leucine methyl ester. Exp Parasitol 68:423–431
Antoine JC, Jouanne C, Ryter A, Benichou JC (1988) Leishmania amazonensis: acidic organelles in amastigotes. Exp Parasitol 67, 287–300
Antoine JC, Jouanne C, Ryter A (1989) Megasomes as targets of leucine methyl ester in Leishmania amazonensis amastigotes. Parasitology 99:1–9
Galvao-Quintao L, Alfieri SC, Ryter A, Rabinovitch M (1990) Intracellular differentiation of Leishmania amazonensis promastigotes to amastigotes: presence of megasomes, cysteine proteinase activity and susceptibility to leucine-methyl ester. Parasitology 101:7–1
Glew RH, Saha AK, Das S & Remaley AT (1988) Biochemistry of theLeishmania species. Microbiol Reviews 52:412–432
Goldman R, Naider F (1974) Permeation and stereospecificity of hydrolysis of peptide esters within intact lysosomes in vitro. Biochim Biophys Acta 338:224–233
Hunter CA, Macpherson LM, Coombs GH (1989) Antileishmanial activity of L-leucine ester and L-tryptophanamide, in Leishmaniasis, DT Hart, ed, Plenum Press, NY pp 741–747
North MJ, Mottram JC, Coombs GH (1990) Cysteine proteinases of parasitic protozoa. Parasitol Today 6:270–275
Pupkis MF, Tetley L, Coombs GH (1986) Leishmania mexicana: amastigote hydrolases in unusual lysosomes. Exp Parasitol 62:29–39
Rabinovitch M, Zilberfarb V, Ramazeilles C (1986) Destruction of Leishmania mexicana amazonensis amastigotes within macrophages by lysosomotropic amino acid esters. J Exp Med 163:520–535
Rabinovitch M, Alfieri SC (1987) From lysosomes to cells, from cells to Leishmania: amino acid esters as potential chemotherapeutic agents. Brazilian J Med Biol Res 20:665–674
Rabinovitch M, Zilberfarb V, Pouchelet M (1987) Leishmania mexicana: destruction of isolated amastigotes by amino acid esters. Am J Trop Med Hyg 36:288–293
Rabinovitch M, Zilberfarb, V (1988) Destruction of intracellular and isolated Leishmania mexicana amazonensis amastigotes by amino acid amides. Parasitology 96:289–296
Rabinovitch M (1989) Leishmanicidal activity of amino acid and peptide esters. Parasitol Today 5:299–301
Ramazeilles C, Rabinovitch M (1989)Leishmania amazonensis: uptake and hydrolysis of 3H amino acid methyl esters by isolated amastigotes. Exp Parasitol 68:135–143
Ramazeilles C, Juliano L, Chagas JR, Rabinovitch M (1990) The antileishmanial activity of dipeptide esters on Leishmania amazonensis amastigotes. Parasitology 100:201–207
Ransom JT, Reeves JP (1983) Accumulation of amino acids within intracellular lysosomes of rat polymorphonuclear leukocytes incubated with amino acid methyl esters. J Biol Chem 258:9270–9275
Thiele DL, Lipsky PE (1990 a) Mechanism of L-leucyl-L-leucine methyl ester-mediated killing of cytotoxic lymphocytes: Dependence on a lysosomal thiol protease, dipeptidyl peptidase I, that is enriched in these cells. Proc Nat Acad Sci USA 87:83–87
Thiele DL, Lipsky PE (1990 b) The action on leucyl-leucine methyl ester on cytotoxic lymphocytes requires uptake by a novel dipeptide-specific facilitated transport system and dipeptidyl peptidase I-mediated conversion to membranolytic products. J Exp Med 172:183–194
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© 1992 Springer-Verlag Berlin Heidelberg
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Rabinovitch, M. et al. (1992). Lysosomes of Leishmania Mexicana Sp. as Targets for Potential Therapeutic Agents. In: Courtoy, P.J. (eds) Endocytosis. NATO ASI Series, vol 62. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-84295-5_60
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DOI: https://doi.org/10.1007/978-3-642-84295-5_60
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