Tat-braftide peptide

Tat-braftide peptide

• Handling and Storage of Synthetic Peptides
• Material Safety Data Sheets (MSDS)

GRKKRRQRRRPQXTRHVNILLFM, X is PEG (-NH-CH2-CH2-O-CH2-CH2-O-CH2-C=O-)

H-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-Pro-Gln-PEG-Thr-Arg-His-Val-Asn-Ile-Leu-Leu-Phe-Met-OH

22

95.25%

C₁₂₈H₂₂₇N₅₁O₃₀S

2990.47

Synthetic

Powder

Tat-braftide is a BRAF kinase inhibitor consisting of the10-mer peptide inhibitor, braftide, TRHVNILLFM, linked by PEG to the cell penetrating sequence TAT. Tat-braftide was designed to bind to the dimer interface of the BRAF kinase domain, and accordingly it inhibits BRAF kinase activity by disrupting BRAF dimers, with an IC50 of 43 nM in kinase assays. Additionally, targeting the dimer interface of BRAF kinase leads to protein degradation of both RAF and MEK, uncovering a novel scaffolding function of RAF in protecting large MAPK complexes from protein degradation. Tat-braftide shows efficient inhibition and degradation of WT BRAF and BRAFG469A in a variety of cells exhibiting either RAS dependence or independence. Tat−braftide treatment causes dose dependent inhibition of growth of HCT116 and HCT-15 cells, with EC50 values of 7.1 and 6.6 μM, demonstrating potent inhibiton of cell viability in KRAS-mutated colon cancer cells.

Normally, this peptide will be delivered in lyophilized form and should be stored in a freezer at or below -20 °C. For more details, please refer to the manual:Handling and Storage of Synthetic Peptides

• Gunderwala et al (2019) Development of Allosteric BRAF Peptide Inhibitors Targeting the Dimer Interface of BRAF. ACS Chem Biol. 14(7) 1471 PMID: 31243962
• Cope et al (2020) Analyses of the oncogenic BRAFD594G variant reveal a kinase-independent function of BRAF in activating MAPK signaling. J Biol Chem. 295(8) 2407 PMID: 31929109

Trifluoroacetic acid (TFA) has a significant impact on peptides due to its role in the peptide synthesis process.

TFA is essential for the protonation of peptides that lack basic amino acids such as Arginine (Arg), Histidine (His), and Lysine (Lys), or ones that have blocked N-termini. As a result, peptides often contain TFA salts in the final product.

TFA residues, when present in custom peptides, can cause unpredictable fluctuations in experimental data. At a nanomolar (nM) level, TFA can influence cell experiments, hindering cell growth at low concentrations (as low as 10 nM) and promoting it at higher doses (0.5–7.0 mM). It can also serve as an allosteric regulator on the GlyR of glycine receptors, thereby increasing receptor activity at lower glycine concentrations.

In an in vivo setting, TFA can trifluoroacetylate amino groups in proteins and phospholipids, inducing potentially unwanted antibody responses. Moreover, TFA can impact structure studies as it affects spectrum absorption.