Disease relevance of N-DL-Leucyl-DL-leucine

• However, transfer of CD8-negative, L-leucyl-L-leucine methyl ester-resistant T helper cells alone was sufficient to generate destructive cholangitis in class I+II major histocompatibility complex-disparate or multiple non-major histocompatibility complex antigen-disparate strain combinations.(ABSTRACT TRUNCATED AT 250 WORDS)[1]
• Treatment of C57BL/6J (B6) murine splenocytes with L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) selectively removes NK cells, CTL precursors, and the capacity to cause lethal graft-vs-host disease (GVHD) in irradiated B6 X DBA/2 F1 mice [2].
• The selective cytotoxicity of the lysosomotropic methyl esters of leucine or its lysosomal condensation product leucyl-leucine has been used to investigate the effect of cytolytic cells on the clonal outgrowth, cellular proliferation and antibody secretion of Epstein-Barr virus (EBV)-transformed human B cells [3].
• Activation and inhibition of a purified aminopeptidase from Brevibacterium linens was investigated using L-alpha-leucyl-4-nitroanilide and L-leucyl-L-leucine as substrates [4].

High impact information on N-DL-Leucyl-DL-leucine

• Treatment of C57BL/6J (B6) splenocytes with L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) selectively removes natural killer cells, cytotoxic T lymphocyte (CTL) precursors, and the capacity to cause lethal GVHD in irradiated B6xDBA/2 F1 (B6D2F1) mice while preserving T helper cell function [5].
• Prevention of lethal murine graft versus host disease by treatment of donor cells with L-leucyl-L-leucine methyl ester [6].
• Exposure of murine or human lymphocytes to L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) results in selective killing of cytotoxic lymphocytes, whereas helper T cells and B cells remain functionally intact [7].
• DC were enriched when purified by standard techniques from non-T cells that were treated with L-leucyl-L-leucine methyl ester, known to be toxic to monocytes and cytolytic cells [8].
• L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) is selectively toxic for human natural killer (NK) cells and cytotoxic T lymphocytes (CTL) at both the precursor and effector stage of differentiation [9].

Biological context of N-DL-Leucyl-DL-leucine

• Sensitivity to L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) was used to characterize the phenotype of human activated killer cells [10].
• Incubation with L-leucyl-L-leucine methyl ester (which removes NK cells, Tc, and precursor Tc) had no effect on the capacity of either C57BL/6J BMC or BALB/cxC57BL/6J F1 BMC or SC to establish chimerism and induce skin graft tolerance [11].
• Synthesis, photoreactivity and cytotoxic activity of caged compounds of L-leucyl-L-leucine methyl ester, an apoptosis inducer [12].
• The effect of various concentrations of antigen, time kinetics, effect of serum, and leucyl-leucine O-methyl ester treatment on the in vitro-immunization system has been studied [13].
• An in vitro immunization (IVI) protocol enables antigen specific antibody production from L-Leucyl-L-Leucine methyl ester (LLME)-treated human peripheral blood lymphocytes (PBL) upon antigen stimulation in the presence of IL-2, IL-4, and muramyl dipeptide [14].

Anatomical context of N-DL-Leucyl-DL-leucine

• Lethal graft-vs-host disease across major histocompatibility barriers: requirement for leucyl-leucine methyl ester sensitive cytotoxic T cells [9].
• Treatment of murine lymphocytes with L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) selectively removes natural killer cells, cytotoxic T lymphocyte precursors, and the capacity to cause lethal graft-vs-host disease, whereas bone marrow stem cell function and alloantigen-induced L3T4+ T helper function remains intact [15].
• Effects of the immunosuppressive dipeptide L-leucyl-L-leucine O-methyl ester on epidermal Langerhans cells [16].
• BMC mediating the veto effect were found to be resistant to L-leucyl-L-leucine methyl ester (Leu-leu-OMe), which excluded BMC-mediated cytotoxicity by NK or lymphokine-activated killer cells, CTL, or activated macrophages [17].
• 2. A number of amino acids (glycine, L-proline and L-leucine) and small peptides (carnosine, glycyl-L-proline, L-leucyl-L-leucine, glycylglycine and glycylglycylglycine) depolarized the brush-border membrane [18].

Associations of N-DL-Leucyl-DL-leucine with other chemical compounds

• Nitrogen absorption from isonitrogenous solutions of L-leucyl-L-leucine and L-leucine: a study in the isolated perfused rat small intestine [19].
• The purpose of the present study was to investigate the utilisation of vascularly administered leucyl-leucine (Leu-Leu), alanyl-glutamine (Ala-Gln) and glycyl-glutamine (Gly-Gln) by the isolated vascularly perfused rat small intestine [20].
• The results suggested that at pH 5, uptake of L-alanyl-L-alanine, like that of L-valyl-L-valine and L-leucyl-L-leucine, was the result of two processes, uptake of intact peptide and uptake of free amino acid released extracellularly [21].
• Two types of immunosuppressants, cycloprodigiosin hydrochloride (cPrG) and L-leucyl-L-leucine methyl ester (LeuLeuOMe), both have the ability to selectively inhibit the lysosomal function, and a related compound to cPrG, prodigiosin 25-C, and LeuLeuOMe have been reported to selectively inhibit the T cell function in vitro [22].
• Lysine, glutamic acid, leucine, leucyl-leucine, or leucyl-leucyl-leucine was inserted between positions 28 and 29 of the alpha-amylase signal peptide using site directed mutagenesis [23].

Gene context of N-DL-Leucyl-DL-leucine

• L-Leucyl-L-leucine methyl ester (LLME) is a lysosomatropic compound that is converted by dipeptidyl peptidase I to metabolites that are membranolytic for cytotoxic T cells, NK cells, and LAK cells [24].
• Characterization of the in vitro sensitivity of human lymphoid and hematopoietic progenitors to L-leucyl-L-leucine methyl ester [25].
• Both dehydropeptidase-I and aminopeptidase-M were capable of hydrolyzing L-leucyl-L-leucine with a Km valve of 1.1 mM and 1.7 mM, respectively, although the hydrolyzing activity of aminopeptidase-M was much higher than that of dehydropeptidase-I [26].
• Renin (EC 3.4.99.19) from both primates and non-primates cleaves this peptide at the leucylleucine bond [27].
• Treatment of donor cells with L-leucyl-L-leucine methyl ester prevents induction of graft-vs-host-like reaction in [lpr/lpr----+/+] chimera [28].

Analytical, diagnostic and therapeutic context of N-DL-Leucyl-DL-leucine

• Thin-layer chromatography and mass spectral analysis revealed that this NK-toxic product was L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) [29].
• The role of leucyl-leucine methyl ester-sensitive cytotoxic cells in skin allograft rejection [30].
• Incubation of canine marrow and peripheral blood mononuclear cells with L-leucyl-L-leucine methyl ester resulted in the inhibition of mitogen- and alloantigen-induced blastogenesis, the elimination of allosensitized CTL and NK activity, and prevented the development of CTL from pCTL [31].
• This inhibitory activity is abolished after treatment of peripheral blood mononuclear cells or purified CD4+ T cells with L-leucyl-L-leucine methyl ester [32].
• L-leucyl-L-leucine methyl ester (LLME) prevents GVHD in several animal models by depleting dipeptidyl peptidase I (DPPI)-expressing cytotoxic cellular subsets [33].

References