Home>>Signaling Pathways>> Proteases>> Endogenous Metabolite>>L-Leucyl-L-Leucine methyl ester (hydrochloride)

L-Leucyl-L-Leucine methyl ester (hydrochloride)

(Synonyms: LLOMe hydrochloride; Leu-Leu methyl ester hydrochloride; H-Leu-Leu-OMe hydrochloride) 目录号 : GC44079

An immunosuppressant

L-Leucyl-L-Leucine methyl ester (hydrochloride) Chemical Structure

Cas No.:6491-83-4

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100mg
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产品描述

L-Leucyl-L-Leucine methyl ester (LLME) is a lysosomal condensation product that has been reported to be cytotoxic towards natural killer cells and CD4+ and CD8+ T lymphocytes without affecting helper T cells and B cells. [1] [2] It has also been shown to induce death of monocytes, polymorphonuclear leukocytes, and myeloid tumor cells. [2] Upon entry into cells via receptor-mediated endocytosis, LLME undergoes a condensation process catalyzed by dipeptidyl peptidase I (DPPI) in lysosomes. This condensation leads to lysosomal rupture and DNA fragmentation in DPPI-expressing immune cells such as cytotoxic T cells and natural killer cells. [2] 

Reference:
[1]. Ohlin, M., Danielsson, L., Carlsson, R., et al. The effect of leucyl-leucine methyl ester on proliferation and Ig secretion of EBV-transformed human B lymphocytes. Immunology 66(4), 485-490 (1989).
[2]. Thiele, D.L., and Lipsky, P.E. 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. Proceedings of the National Academy of Sciences of the United States of America 87(1), 83-87 (1990).

Chemical Properties

Cas No. 6491-83-4 SDF
别名 LLOMe hydrochloride; Leu-Leu methyl ester hydrochloride; H-Leu-Leu-OMe hydrochloride
化学名 L-leucyl-L-leucine, methyl ester, monohydrochloride
Canonical SMILES COC([C@@H](NC([C@@H](N)CC(C)C)=O)CC(C)C)=O.Cl
分子式 C13H26N2O3•HCl 分子量 294.8
溶解度 30mg/mL in DMSO, 10mg/mL in DMF, 30mg/mL in Ethanol 储存条件 Store at -20°C
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1 mM 3.3921 mL 16.9607 mL 33.9213 mL
5 mM 0.6784 mL 3.3921 mL 6.7843 mL
10 mM 0.3392 mL 1.6961 mL 3.3921 mL
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Research Update

Induction of apoptosis of activated murine splenic T cells by cycloprodigiosin hydrochloride, a novel immunosuppressant

Immunopharmacology 2000 Jan;46(1):29-37.PMID:10665777DOI:10.1016/s0162-3109(99)00153-8

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. We therefore examined the cell-type specificity of cPrG and LeuLeuOMe using murine splenocytes. Concanavalin A (Con A)- and lentil lectin-induced proliferation was suppressed by cPrG more profoundly than lipopolysaccharide-induced proliferation. At the optimal concentration, Con A induced the proliferation of both CD4+ and CD8+ cells, whereas at a supra-optimal concentration Con A induced rather selective proliferation of CD8+ cells. Irrespective of the dose of Con A, CD4+ and CD8+ cells were equally affected by cPrG. In contrast, LeuLeuOMe induced the selective loss of CD8+ cells. cPrG enhanced the apoptosis of murine splenocytes and nylon fiber column-purified T cells cultured in the presence of Con A, as shown by the decrease in cell size and/or DNA fragmentation. Overall, this study revealed that the cell-type specificity of cPrG is different from that of LeuLeuOMe, and that the immunosuppression by cPrG is associated with apoptosis.