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506048 Beclin-1 Activator I, TAT-Beclin-1 - Calbiochem

506048
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Overview

Replacement Information

Key Specifications Table

Empirical Formula
C₁₆₄H₂₅₁N₅₇O₄₅

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      Description
      OverviewA cell-permeable Atg6/Beclin1-derived autophagy-inducing peptide (Minimum effective conc. ≤10 µM for 3 h) that effectively activates cellular Beclin1 by competing against Beclin1 for binding to its negative regulator GAPR-1/GLIPR2 on the Golgi surface. Shown to induce autosis, autophagy-dependent death, in cells of human, rat, and murine origin in a dose- and time-dependent manner (Minimum effective conc. >5 µM for 5 h in HeLa cultures), blockable by autophagy inhibitor 3-MA (10 mM, Cat. no.189490; [T-B] = 20 µM) or via Na+/K+-ATPase inhibition, but insensitive to Z-VAD-FMK (Cat. no. 219007) or Nec-1 (Cat. nos. 480065 & 505224) treatment. Non-cytotoxic autophagy induction with lower doses of Tat-Beclin1 and shorter exposure times is therapeutically beneficial in blocking RNA viral replications both in cultures (4 h 10 µM peptide treatment 4 h post viral infection in HeLa cultures; 0.5-5 µM peptide pre-treatment 24 h before HIV infection in human MDM cultures) in vitro and in CHIKV-infected 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. Note: increased drug potency is reported in acidified (pH 7.0) serum-free cultures.
      Catalogue Number506048
      Brand Family Calbiochem®
      SynonymsAtg6 Activator I, Beclin1-GAPR-1 Interaction Blocker I, Vps30 Activator I, H₂N-YGRKKRRQRRR-GG-TNVFNATFEIWHDGEFGT-CO₂H, Autophagy Inducer IV
      References
      ReferencesLiu, Y., et al. 2013. Proc. Natl. Acad. Sci. USA 110, 20634.
      Shoji-Kawata, S., et al. 2013. Nature. 494, 201.
      Product Information
      DeclarationSold under license of US Patent 8,722,628.
      FormWhite powder
      FormulationSupplied as a trifluoroacetate salt.
      Hill FormulaC₁₆₄H₂₅₁N₅₇O₄₅
      Chemical formulaC₁₆₄H₂₅₁N₅₇O₄₅
      Hygroscopic Hygroscopic
      ReversibleY
      Quality LevelMQ100
      Applications
      ApplicationBeclin-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.
      Biological Information
      Primary TargetGAPR-1/GLIPR2
      Purity≥97% by HPLC
      Physicochemical Information
      Cell permeableY
      Peptide SequenceH-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
      Dimensions
      Materials Information
      Toxicological Information
      Safety Information according to GHS
      Safety Information
      Product Usage Statements
      Storage and Shipping Information
      Ship Code Ambient Temperature Only
      Toxicity Standard Handling
      Storage +2°C to +8°C
      Protect from Light Protect from light
      Hygroscopic Hygroscopic
      Do not freeze Ok to freeze
      Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
      Packaging Information
      Packaged under inert gas Packaged under inert gas
      Transport Information
      Supplemental Information
      Specifications

      Documentation

      Beclin-1 Activator I, TAT-Beclin-1 - Calbiochem SDS

      Title

      Safety Data Sheet (SDS) 

      References

      Reference overview
      Liu, Y., et al. 2013. Proc. Natl. Acad. Sci. USA 110, 20634.
      Shoji-Kawata, S., et al. 2013. Nature. 494, 201.
      Data Sheet

      Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.

      Revision26-February-2015 JSW
      SynonymsAtg6 Activator I, Beclin1-GAPR-1 Interaction Blocker I, Vps30 Activator I, H₂N-YGRKKRRQRRR-GG-TNVFNATFEIWHDGEFGT-CO₂H, Autophagy Inducer IV
      DescriptionA cell-permeable autophagy-inducing peptide (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. Note: increased drug potency is reported in acidified (pH 7.0) serum-free cultures.
      FormWhite powder
      FormulationSupplied as a trifluoroacetate salt.
      Intert gas (Yes/No) Packaged under inert gas
      Chemical formulaC₁₆₄H₂₅₁N₅₇O₄₅
      Peptide SequenceH-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
      Purity≥97% by HPLC
      SolubilityDMSO (50 mg/ml) or H₂O (50 mg/ml)
      Storage +2°C to +8°C
      Hygroscopic
      Protect from light
      Do Not Freeze Ok to freeze
      Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
      Toxicity Standard Handling
      ReferencesLiu, Y., et al. 2013. Proc. Natl. Acad. Sci. USA 110, 20634.
      Shoji-Kawata, S., et al. 2013. Nature. 494, 201.