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MedKoo Cat#: 597431 | Name: Methyl leucylleucinate HCl
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Methyl leucylleucinate HCl 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

Chemical Structure

Methyl leucylleucinate HCl
Methyl leucylleucinate HCl
CAS#6491-83-4 (HCl)

Theoretical Analysis

MedKoo Cat#: 597431

Name: Methyl leucylleucinate HCl

CAS#: 6491-83-4 (HCl)

Chemical Formula: C13H27ClN2O3

Exact Mass: 0.0000

Molecular Weight: 294.82

Elemental Analysis: C, 52.96; H, 9.23; Cl, 12.02; N, 9.50; O, 16.28

Price and Availability

Size Price Availability Quantity
250mg USD 100.00 Ready to ship
500mg USD 150.00 Ready to ship
1g USD 250.00 Ready to ship
2g USD 400.00 Ready to ship
5g USD 750.00 Ready to ship
10g USD 1,250.00 Ready to ship
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Synonym
Methyl leucylleucinate hydrochloride; Leu-Leu-ome HCl; Leucylleucine methyl ester hydrochloride;
IUPAC/Chemical Name
methyl L-leucyl-L-leucinate hydrochloride
InChi Key
RVXQFTNCULOWRV-ACMTZBLWSA-N
InChi Code
InChI=1S/C13H26N2O3.ClH/c1-8(2)6-10(14)12(16)15-11(7-9(3)4)13(17)18-5;/h8-11H,6-7,14H2,1-5H3,(H,15,16);1H/t10-,11-;/m0./s1
SMILES Code
O=C(N[C@@H](CC(C)C)C(OC)=O)[C@H](CC(C)C)N.[H]Cl
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Product Data
Product Data
Certificate of Analysis
View CoA: current batch, Lot#C9B08B19
Safety Data Sheet (SDS)
View Safety Data Sheet (SDS)
Instruction
View handling instruction
Biological target:
L-Leucyl-L-Leucine methyl ester (LLOMe) hydrochloride selectively eliminates lymphocytes with cytotoxic potential.
In vitro activity:
Next, cell-killing potential of LLOMe was evaluated in all five cell lines. In both monocytic cell lines, a substantial amount of cell death was observed 4 h post-LLOMe treatment at 0.25–0.5 mm concentration, whereas significant cell death in U-87-MG cells was only observed after 18 h at LLOMe concentrations ≥ 0.5 mm with essentially no death observed at the 10 h time point. However, in HeLa cells, cell death was only notable after 18 h at 5 mm LLOMe concentration. Reference: FEBS J. 2020 Dec;287(23):5148-5166. https://pubmed.ncbi.nlm.nih.gov/32319717/
In vivo activity:
TBD
Solvent mg/mL mM comments
Solubility
DMSO 30.0 101.76
DMF 10.0 33.92
Ethanol 30.0 101.76
PBS (pH 7.2) 10.0 33.92
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 294.82 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Kavčič N, Butinar M, Sobotič B, Hafner Česen M, Petelin A, Bojić L, Zavašnik Bergant T, Bratovš A, Reinheckel T, Turk B. Intracellular cathepsin C levels determine sensitivity of cells to leucyl-leucine methyl ester-triggered apoptosis. FEBS J. 2020 Dec;287(23):5148-5166. doi: 10.1111/febs.15326. Epub 2020 May 1. PMID: 32319717. 2. Repnik U, Borg Distefano M, Speth MT, Ng MYW, Progida C, Hoflack B, Gruenberg J, Griffiths G. L-leucyl-L-leucine methyl ester does not release cysteine cathepsins to the cytosol but inactivates them in transiently permeabilized lysosomes. J Cell Sci. 2017 Sep 15;130(18):3124-3140. doi: 10.1242/jcs.204529. Epub 2017 Jul 28. PMID: 28754686.
In vitro protocol:
1. Kavčič N, Butinar M, Sobotič B, Hafner Česen M, Petelin A, Bojić L, Zavašnik Bergant T, Bratovš A, Reinheckel T, Turk B. Intracellular cathepsin C levels determine sensitivity of cells to leucyl-leucine methyl ester-triggered apoptosis. FEBS J. 2020 Dec;287(23):5148-5166. doi: 10.1111/febs.15326. Epub 2020 May 1. PMID: 32319717. 2. Repnik U, Borg Distefano M, Speth MT, Ng MYW, Progida C, Hoflack B, Gruenberg J, Griffiths G. L-leucyl-L-leucine methyl ester does not release cysteine cathepsins to the cytosol but inactivates them in transiently permeabilized lysosomes. J Cell Sci. 2017 Sep 15;130(18):3124-3140. doi: 10.1242/jcs.204529. Epub 2017 Jul 28. PMID: 28754686.
In vivo protocol:
TBD
1: Barbierato M, Facci L, Argentini C, Marinelli C, Skaper SD, Giusti P. Astrocyte-microglia cooperation in the expression of a pro-inflammatory phenotype. CNS Neurol Disord Drug Targets. 2013 Aug;12(5):608-18. PubMed PMID: 23574172. 2: Yamashita M, Harada G, Matsumoto SE, Aiba Y, Ichikawa A, Fujiki T, Udono M, Kabayama S, Yoshida T, Zhang P, Fujii H, Shirahata S, Katakura Y. Suppression of immunoglobulin production in human peripheral blood mononuclear cells by monocytes via secretion of heavy-chain ferritin. Immunobiology. 2014 Feb;219(2):149-57. doi: 10.1016/j.imbio.2013.08.011. Epub 2013 Sep 5. PubMed PMID: 24157279. 3: Ohlin M, Danielsson L, Carlsson R, Borrebaeck CA. The effect of leucyl-leucine methyl ester on proliferation and Ig secretion of EBV-transformed human B lymphocytes. Immunology. 1989 Apr;66(4):485-90. PubMed PMID: 2541070; PubMed Central PMCID: PMC1385146. 4: Sakauchi H, Furuta T, Kobayashi Y, Iwamura M. Synthesis and cytotoxic studies of 5-O-(beta-glucopyranosyl)-2-nitrobenzyl caged L-leucyl-L-leucine methyl ester with increased solubility in PBS containing 1% DMSO. Biochem Biophys Res Commun. 1997 Apr 7;233(1):211-5. PubMed PMID: 9144425. 5: Thiele DL, Lipsky PE. Apoptosis is induced in cells with cytolytic potential by L-leucyl-L-leucine methyl ester. J Immunol. 1992 Jun 15;148(12):3950-7. PubMed PMID: 1602138. 6: Li Y, Ashby JM, Eremin O. In vitro primary immunization of B lymphocytes for producing human monoclonal antibodies against tumor-associated antigens. Hum Antibodies Hybridomas. 1993 Jan;4(1):26-30. PubMed PMID: 8431555. 7: Hsieh MH, Varadi G, Flomenberg N, Korngold R. Leucyl-leucine methyl ester-treated haploidentical donor lymphocyte infusions can mediate graft-versus-leukemia activity with minimal graft-versus-host disease risk. Biol Blood Marrow Transplant. 2002;8(6):303-15. PubMed PMID: 12108916. 8: Thiele DL, Geissler GH, Williams FH, Lipsky PE. The role of leucyl-leucine methyl ester-sensitive cytotoxic cells in skin allograft rejection. Transplantation. 1992 Jun;53(6):1334-40. PubMed PMID: 1604489. 9: Thiele DL, Lipsky PE. The action of 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. 1990 Jul 1;172(1):183-94. PubMed PMID: 1972727; PubMed Central PMCID: PMC2188150. 10: Thiele DL, Calomeni JA, Lipsky PE. Leucyl-leucine methyl ester treatment of donor cells permits establishment of immunocompetent parent----F1 chimeras that are selectively tolerant of host alloantigens. J Immunol. 1987 Oct 1;139(7):2137-42. PubMed PMID: 3309052. 11: van Boven A, Konings WN. A Phosphate-Bond-Driven Dipeptide Transport System in Streptococcus cremoris Is Regulated by the Internal pH. Appl Environ Microbiol. 1987 Dec;53(12):2897-902. PubMed PMID: 16347504; PubMed Central PMCID: PMC204219. 12: Thiele DL, Charley MR, Calomeni JA, Lipsky PE. Lethal graft-vs-host disease across major histocompatibility barriers: requirement for leucyl-leucine methyl ester sensitive cytotoxic T cells. J Immunol. 1987 Jan 1;138(1):51-7. PubMed PMID: 2946780. 13: Geeta NS, Ramanadham M. In vitro immunization of murine lymphocytes using immobilized immunogens. Biotechnol Appl Biochem. 1996 Aug;24 ( Pt 1):61-4. PubMed PMID: 8756395. 14: Sublette E, Gintzler AR. Stimulus frequency and intensity: critical determinants of opioid enhancement or inhibition of evoked methionine-enkephalin release. Brain Res. 1992 Dec 18;599(1):165-70. PubMed PMID: 1337301. 15: Poloni A, Leoni P, Buscemi L, Balducci F, Pasquini R, Masia MC, Viola N, Costantino E, Discepoli G, Corradini P, Tagliabracci A, Olivieri A. Engraftment capacity of mesenchymal cells following hematopoietic stem cell transplantation in patients receiving reduced-intensity conditioning regimen. Leukemia. 2006 Feb;20(2):329-35. PubMed PMID: 16341047. 16: Cilloni D, Carlo-Stella C, Falzetti F, Sammarelli G, Regazzi E, Colla S, Rizzoli V, Aversa F, Martelli MF, Tabilio A. Limited engraftment capacity of bone marrow-derived mesenchymal cells following T-cell-depleted hematopoietic stem cell transplantation. Blood. 2000 Nov 15;96(10):3637-43. PubMed PMID: 11071665. 17: McGuire MJ, Lipsky PE, Thiele DL. Purification and characterization of dipeptidyl peptidase I from human spleen. Arch Biochem Biophys. 1992 Jun;295(2):280-8. PubMed PMID: 1586157.