Disease relevance of Leucyl-leucine-methyl ester

• The mechanism of toxicity for cytolytic lymphocytes of Leu-Leu-OMe and related dipeptide derivatives was examined [1].

High impact information on Leucyl-leucine-methyl ester

• In this regard, Leu-Leu-OMe was found to be incorporated by lymphocytes and monocytes via a saturable facilitated transport mechanism with characteristics distinct from previously characterized mammalian dipeptide transport processes [1].
• However, some NK nontoxic DPPI substrates were found to be comparable with Leu-Leu-OMe in avidity for this transport process [1].
• L-leucine methyl ester (Leu-OMe), Leu-Leu-OMe, Phe-OMe, and Glu-(OMe)2 are toxic to mononuclear phagocytes (M phi) and neutrophils [2].
• Depletion of DPPI-enriched cells by treatment with Leu-Leu-OMe resulted in loss of cytolytic effector function from each CTL population [3].
• Thus, killing of cytotoxic lymphocytes and myeloid cells by Leu-Leu-OMe appears to be dependent on generation of metabolites with membranolytic properties, but cell death induced by this process does not involve simple lysis of the plasma membrane [4].

Chemical compound and disease context of Leucyl-leucine-methyl ester

• Previous studies have demonstrated that the selective toxicity of leucyl-leucine methyl ester (Leu-Leu-OMe) for cytotoxic lymphocytes and myeloid cells is dependent on intracellular conversion to membranolytic metabolites by the acyl transferase activity of the granule enzyme dipeptidyl peptidase I (DPPI) that is enriched in these cells [4].

Anatomical context of Leucyl-leucine-methyl ester

• Preincubation with Zn2+, a known inhibitor of endonuclease activity prevented Leu-Leu-OMe-induced 51Cr or [3H]TdR release from these cell lines, but had no effect on antibody + C or Phe-OMe-induced 51Cr release [4].
• Zn2+ also prevented Leu-Leu-OMe-mediated killing of normal human CD16+ NK cells [4].
• When human U937, HL60, or THP-1 myeloid tumor cell lines or murine CTLL-2 cells were treated with Leu-Leu-OMe, early release of both cytosolic 51Cr and soluble [3H]TdR labeled DNA fragments was observed, whereas antibody + C treatment of these cells caused only 51Cr release [4].
• The two major gamma delta T cell subsets V gamma 9+V delta 2+ and V gamma 9-V delta 1+ were equally susceptible to Leu-OMe and Leu-Leu-OMe treatment [5].
• Porcine polymorphonuclear cells (PMN) and murine macrophages (M phi) were treated in vitro with Leu-OMe or Leu-Leu-OMe (1.5-5.0 mM) for various periods of time [6].

Analytical, diagnostic and therapeutic context of Leucyl-leucine-methyl ester

• Six of seven dogs conditioned with 920 cGy total-body irradiation engrafted successfully after receiving autologous marrow that was incubated with Leu-Leu-OMe prior to infusion [7].
• These cumulative results indicate that incubation with Leu-Leu-OMe is a feasible method to deplete canine marrows of alloreactive and cytotoxic T cells prior to transplantation [7].

References