L-Leucyl-L-Leucine methyl ester (hydrochloride) is a lysosomal hydrolysis product that exhibits cytotoxicity towards natural killer cells and CD4+ and CD8+ T lymphocytes, but does not affect helper T cells or B cells[1, 2]. L-Leucyl-L-Leucine methyl ester (hydrochloride) is a lysosomal disruptor that induces lysosomal pathway stress[3, 4].
In vitro, treatment of mouse embryonic fibroblasts (MEFs) with L-Leucyl-L-Leucine methyl ester (hydrochloride) (1mM) for 0-8h enhances LRRK2 (leucine-rich repeat kinase 2)-mediated phosphorylation of Rab10 and Rab12[5].
References:
[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[J]. Immunology, 1989, 66(4): 485.
[2] Thiele D L, 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[J]. Proceedings of the National Academy of Sciences, 1990, 87(1): 83-87.
[3] Alvarez-Valadez K, Sauvat A, Diharce J, et al. Lysosomal damage due to cholesterol accumulation triggers immunogenic cell death[J]. Autophagy, 2025, 21(5): 934-956.
[4] Lau T T A. Engineering a pro-apoptotic BCG strain to improve efficacy of the current tuberculosis vaccine[D]. University of British Columbia, 2017.
[5] Kalogeropulou A F, Freemantle J B, Lis P, et al. Endogenous Rab29 does not impact basal or stimulated LRRK2 pathway activity[J]. Biochemical Journal, 2020, 477(22): 4397-4423.
L-Leucyl-L-Leucine methyl ester (hydrochloride)是一种溶酶体缩合产物，对自然杀伤细胞和CD4+及CD8+ T淋巴细胞具有细胞毒性，但不影响辅助性T细胞和B细胞[1, 2]。L-Leucyl-L-Leucine methyl ester (hydrochloride)是一种溶酶体扰动剂，能够诱导溶酶体途径应激[3, 4]。
在体外，L-Leucyl-L-Leucine methyl ester (hydrochloride)（1mM）处理小鼠胚胎成纤维细胞（MEFs）0-8h，增强了LRRK2（leucine-rich repeat kinase 2）介导的Rab10和Rab12磷酸化作用[5]。