BRC4wt peptide

BRC4wt peptide

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

Batch to batch variation of the purity

Ac-LLGFHTASGKKVKIAK-NH2

Ac-Leu-Leu-Gly-Phe-His-Thr-Ala-Ser-Gly-Lys-Lys-Val-Lys-Ile-Ala-Lys-NH2

16

95.03%

C₈₁H₁₃₉N₂₃O₁₉

1739.11

Synthetic

Powder

BRC4wt is a peptide derived from the BRC4 repeat motif of the BReast CAncer gene 2 (BRCA2) protein, which is able to prevent the DNA repair protein RAD51 binding to BRCA2. Cancer cells rely on efficient DNA repair to survive and proliferate and the BRCA2 tumour suppressor protein is indispensable for repair of DNA double-strand breaks through promotion of RAD51 loading onto single-stranded DNA. Through blockade of this interaction BRC4wt inhibits camptothecin and ionising radiation induced RAD51 foci formation and homologous recombination in cancer cells. BRC4wt can impair the replication fork-protective function of BRCA2 and trigger double-strand break repair protein MRE11 dependent degradation of nascent DNA in response to replication stress. A BRC4wt cell penetrating peptide derivative confers selective hypersensitivity to PARP inhibition in cancer cells but spares noncancerous cells, giving it potential as a radio and chemosensitiser.

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

• Trenner et al (2018) A Short BRCA2-Derived Cell-Penetrating Peptide Targets RAD51 Function and Confers Hypersensitivity toward PARP Inhibition. Mol Cancer Ther. 17(7) 1392 PMID: 29654063

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.