Larazotide Acetate |CAS 881851-50-9|DC Chemicals

Cas No.:	881851-50-9
Chemical Name:	Larazotide acetate
Synonyms:	acetic acid,2-[[(2S)-1-[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-5-oxopentanoyl]pyrrolidine-2-carbonyl]amino]acetic acid;Larazotide acetate;Larazotide (acetate);Larazotide acetate [USAN];Larazotide acetate (USAN);Glycine, glycylglycyl-L-valyl-L-leucyl-L-valyl-L-glutaminyl-L-prolyl-, monoacetate;FO8S2IW40N;A16916;D09352;Q25327025;Glycylglycyl-L-valyl-L-leucyl-L-valyl-L-glutaminyl-L-prolylglycine acetate
SMILES:	O=C([C@]([H])(C([H])([H])C([H])([H])C(N([H])[H])=O)N([H])C([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C([C@]([H])(C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C(C([H])([H])N([H])C(C([H])([H])N([H])[H])=O)=O)=O)=O)=O)N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(N([H])C([H])([H])C(=O)O[H])=O.O([H])C(C([H])([H])[H])=O
Formula:	C₃₄H₅₉N₉O₁₂
M.Wt:	785.8854
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Larazotide acetate is a synthetic peptide that functions as a tight junction regulator and reverses leaky junctions to their normally closed state.
Target:	Paracellular permeability
In Vivo:	When tested in vivo in gliadin-sensitized HLA-HCD4/DQ8 double transgenic mice, larazotide acetate inhibits gliadin-induced macrophage accumulation in the intestine and preserved normal tight junction structure.
In Vitro:	Larazotide acetate inhibits the redistribution and rearrangement of zonula occludens-1 (ZO-1) and actin caused by AT-1002 and gliadin fragments in Caco-2 and IEC6 cells. Larazotide acetate inhibits the AT-1002-induced TEER reduction and TJ opening in Caco-2 cells. Larazotide acetate inhibits the translocation of a gliadin 13-mer peptide, which has been implicated in celiac disease, across Caco-2 cell monolayers. Further, apically applied Larazotide acetate inhibits the increase in TJ permeability elicited by basolaterally applied cytokines.
Cell Assay:	Caco-2 cells are seeded onto 12-well plate and grown for 21–28 days until fully differentiated. The apical and basolateral compartments of Caco-2 cell monolayers are pre-incubated in Hank’s Balanced Salt Solution (HBSS) at 37°C for 30 min. Treatment solutions containing 7.5 mM LY with or without AT-1002 (7 mM) and different concentrations of larazotide acetate (5, 10, 12.5, 15 mM) in HBSS are added to the apical compartment of each monolayer and incubated at 37°C, 50 rpm for 180 min. At the end of the incubation, samples are removed from the basolateral compartment and analyzed in a fluorescence plate reader at excitation and emission wavelengths of 485 nm and 535 nm, respectively. The increase in LY passage is calculated for each treatment and is expressed relative to that of untreated controls.
Animal Administration:	Mice[1] Cohorts of HLA-HCD4/DQ8 mice (n=10 each) are sensitized (i.p.) with 500 μg of gliadin dissolved in 0.02 mM acetic acid in 50 μg of Complete Freund’sAdjuvant; thereafter, mice are gavaged with gliadin (2 mg/mouse), +/− treatment, 2×/week for 7 weeks. Group 1 receives larazotide acetate (250 μg/mouse) and gliadin, Group 2 receives AT-1002 (250 μg/mouse) and gliadin, and Group 3 is gavaged with gliadin only. A group of non-sensitized controls (CFA, i.p. only) is gavaged with rice. Twenty-four hours after the last gavage, small intestinal tissue is mounted in Ussing chambers for the measurement of electrical parameters (Isc, conductance) and macromolecule transport (horseradish peroxidase [HRP] flux). Tissue is processed for macrophage counts by immunohistochemistry using F4/80 antibody specific for a macrophage-restricted cell surface glycoprotein.
References:	[1]. Gopalakrishnan S, et al. Larazotide acetate regulates epithelial tight junctions in vitro and in vivo.

MSDS

Cat. No.	Product name	Field of application
DC12145	DLinDMA	DLinDMA is a key lipid component of stable nucleic acid lipid particles as a benchmark.
DC40169	DMG-PEG2000(C14-PEG2000)	DMG-PEG 2000 is used for the preparation of liposome for siRNA delivery with improved transfection efficiency in vitro. DMG-PEG 2000 is also used for the lipid nanoparticle for an oral plasmid DNA delivery approach in vivo through a facile surface modific
DC45611	DMPC	1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) is a synthetic phospholipid used in liposomes. 1,2-Dimyristoyl-sn-glycero-3-phosphocholine is used for the study of lipid monolayers and bilayers.
DC70000	Lysyllysyllysine	Lysyllysyllysine is a cationic moietie that may be used in the construction of gene delivery vectors and DNA nanoparticles.
DC33580	DODMA	DODMA, also known as MBN 305A is a a cationic lipid containing the unsaturated long-chain (18:1) oleic acid inserted at both the sn-1 and sn-2 positions. It has been used in the composition of lipospomes formulated as stable nucleic acid lipid particles that can encapsulate siRNA or other small molecules to be used for drug delivery
DC33635	DODAP	DODAP, also known as 1,2-Dioleoyl-3-dimethylammonium-propane, is a cationic lipid. It has been used as a component in liposomes that can be used to encapsulate siRNA, immunostimulatory oligodeoxynucleotides, antisense oligonucleotides, or chemotherapeutic agents for in vitro and in vivo delivery.
DC59010	C14-4 (C14-494,Lipid B-4,Lipid B4)	C14-4 (C14-494,Lipid B-4,Lipid B4) is a novel ionizable lipid with the highest T-cell transfection efficiency and low cytotoxicity.The C14-4 ionizable lipid has been explored for CAR-T therapy.To screen the excellent formulations for mRNA delivery, a lipid library of 24 ionizable lipids was constructed to make iLNPs, which were used to deliver luciferase mRNA into Jurkat cells.[115] The optimal iLNPs formulation was C14-4 iLNPs (C14-4 ionizable lipid, DOPE, chol, and PEG at a molar ratio of 35%, 16%, 46.5%, and 2.5%) (Figure 6c). The optimal dose of luciferase mRNA for C14-4 iLNPs was 30 ng. Compared with electroporated CAR T cells, the CAR T cells engineered via C14-4 iLNPs showed potent cancer-killing activity when they were cocultured with Nalm-6 acute lymphoblastic leukemia cells. To obtain a safer and more effective CAR mRNA delivery vehicle, the orthogonal design provided 256 potential formulations, and 16 representative iLNPs formulations were evaluated.Through evaluating the safety, delivery efficiency, and transfection efficiency of 16 iLNPs, the formulation B10 (C14-4 ionizable lipid, DOPE, chol, PEG at a molar ratio of 40%, 30%, 25%, and 2.5%) was screened out as the optimal performing formulation. The luciferase expression based on B10 formulation was increased threefold than the initial formulation. Reducing the accumulation and clearance of iLNPs in the liver can increase the expression of CAR mRNA in T cells, further improving the therapeutic effect of CAR-T. Studies have shown that cholesterol analogs can alter the mechanisms of intracellular circulation and enhance the delivery of mRNA, which may be related to the reduced recognition of iLNPs by the Niemann Pick C1 (NPC1) enzyme.The addition of a hydroxyl group to various locations in the cholesterol molecule can alter the binding kinetics between the modified cholesterol and NPC1, and reduced NPC1 recognition of cholesterol. The results showed that replacement of 25% and 50% 7 α-hydroxycholesterol for cholesterol in iLNPs improved mRNA delivery to primary human T cells in vitro by 1.8-fold and twofold, respectively.C14-4 is one of the ionizable lipids to efficiently deliver mRNA to Jurkat cells or primary human T cells. It will effectively promote the development of mRNA delivery by iLNPs for CAR-T therapy.
DC33636	DOTAP	DOTAP, also known as 1,2-Dioleoyl-3-trimethylammoniumpropane, is a cationic liposome-forming compound used for transfection of DNA, RNA, and other negatively charged molecules into eukaryotic cells. It has been used in gene delivery vectors for gene ther
DC58047	DSPE-PEG 2000	PEG2000-DSPE is used for creating micelles that are able to carry drugs with low solubility.
DC31000	LP-01	LP-01 is an ionizable cationic amino lipid (pKa = ~6.1). It has been used in the generation of lipid nanoparticles (LNPs). LNPs containing LP-01 and encapsulating both Cas9 mRNA and modified single-guide RNA (sgRNA) for the transport protein transthyretin (Ttr) induce gene editing in liver cells in mice in a dose-dependent manner resulting in reduced serum Ttr levels for at least 12 months.