5.06048

TAT-Beclin-1

≥97% (HPLC), powder, Beclin-1 activator, Calbiochem^®

• Synonim(y): Beclin-1 Activator I, TAT-Beclin-1, Atg6 Activator I, Beclin1-GAPR-1 Interaction Blocker I, Vps30 Activator I, H₂N-YGRKKRRQRRR-GG-TNVFNATFEIWHDGEFGT-CO₂H, Autophagy Inducer IV
• Wzór empiryczny (zapis Hilla): C₁₆₄H₂₅₁N₅₇O₄₅
• Masa cząsteczkowa: 3741.10
• Kod UNSPSC: 12352200
• NACRES: NA.77

Właściwości

• product name: Beclin-1 Activator I, TAT-Beclin-1,
• Próba: ≥97% (HPLC)
• Poziom jakości: 100
• Postać: powder
• producent / nazwa handlowa: Calbiochem^®
• warunki przechowywania: OK to freeze; desiccated (hygroscopic); protect from light
• kolor: white
• rozpuszczalność: DMSO: 50 mg/mL; water: 50 mg/mL
• temp. przechowywania: 2-8°C

Opis

Opis ogólny

Beclin-1 Activator I, TAT-Beclin-1, is a cell-permeable Atg6/Beclin1-derived autophagy-inducing peptide. Activates Beclin1 by competing against its negative regulator GAPR-1/GLIPR2. TAT-Beclin-1 (Minimum effective conc. ≤10 µM assessed by increased LC3-II/LC3-I ratio & p62 downregulation post 3 h treatment in A549, COS-7, HBEC30-KT, HCC827, HeLa, MEF, THP-1 cultures) that is composed of essential HIV-1 virulence factor Nef-binding sequence derived from human Atg6/Beclin1 (aa 267-284) evolutionarily conserved domain (ECD) with substitutions at three non-species-conserved residues (H275E, S279D, and Q280E) for enhanced solubility and N-terminally fused to the membrane-permeant HIV-1 Tat protein transduction domain (PTD) sequence (aa 47-57) via a -Gly-Gly- linkage to facilitate cellular delivery and Beclin1 activation via competitive binding to its negative regulator "Golgi-associated plant pathogenesis-related protein-1" (GAPR-1/GLIPR2) on the Golgi surface. Shown to effectively induce autosis, autophagy-dependent death morphologically and pharmacologically distinct from apoptosis and necrosis, in various cell cultures of human, rat, and murine origin in a dose- and time-dependent manner (Minimum effective conc. >5 µM post 5 h treatment as assessed by HeLa Trypan blue staining; Fold of control Trypan blue-positive population/20 µM peptide exposure time = 3/1 h, 9/4 h, 20/8 h), blockable by autophagy inhibitor 3-MA (10 mM, Cat. no. 189490; [T-B] = 20 µM) or via Na+/K+-ATPase inhibition by cardiac glycosides, but insensitive to Z-VAD-FMK (Cat. no. 219007) or Nec-1 (Cat. nos. 480065 & 505224) treatment. Autophagy induction by Tat-Beclin1 treatment is also reported to result in clearance of small (<1 µm) CFP-htt103Q aggregates in HeLa cells (59% and 85% reduction, respectively, of aggregates-positive population and average aggregates per cell; 20 µM/4h/d for 2 d) and non-cytotoxic autophagy induction with lower level of Tat-Beclin1 dosage and limited exposure time is demonstrated to be therapeutically beneficial in blocking RNA viral replications both in cultures (4 h, 10 µM peptide treatment 4 h post CHIKV, SINV, or WNV infection in HeLa cultures; 0.5-5 µM peptide pre-treatment 24 h prior to HIV infection in human MDM cultures) in vitro and in CHIKV-inoculated neonatal mice (15 mg/kg/day i.p.) in vivo. While Tat-Beclin1 bioavailability is limited to the peripheral tissues in mice, a peptide based on Tat-Beclin1 retro-inverso sequence (Cat. no. 506416) shows efficacy in a murine model of neonatal WNV CNS infection.

Działania biochem./fizjol.

Cell permeable: yes

Primary Target
GAPR-1/GLIPR2

Reversible: yes

Opakowanie

Packaged under inert gas

Ostrzeżenie

Toxicity: Standard Handling (A)

Sekwencja

H-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg~Gly-Gly~Thr-Asn-Val-Phe-Asn-Ala-Thr-Phe-Glu-Ile-Trp-His-Asp-Gly-Glu-Phe-Gly-Thr-OH

Postać fizyczna

Supplied as a trifluoroacetate salt.

Rekonstytucja

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Inne uwagi

Increased drug potency is reported in acidified (pH 7.0) serum-free cultures.

Informacje prawne

Sold under license of US Patent 8,722,628.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

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Informacja o środkach bezpieczeństwa

• Kod klasy składowania: 11 - Combustible Solids
• Klasa zagrożenia wodnego (WGK): WGK 1
• Temperatura zapłonu (°F): Not applicable
• Temperatura zapłonu (°C): Not applicable