KRpep-2d peptide

KRpep-2d peptide

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

Ac-RRRRCPLYISYDPVCRRRR-NH2, disulfide bridge between cysteines 5 and 15

Ac-Arg-Arg-Arg-Arg-Cys-Pro-Leu-Tyr-Ile-Ser-Tyr-Asp-Pro-Val-Cys-Arg-Arg-Arg-Arg-NH2

19

95.22%

C₁₀₈H₁₈₂N₄₄O₂₅S₂

2561

Synthetic

Powder

KRpep-2d is a potent K-Ras inhibitor, discovered after optimization of an initial hit obtained by phage display technology. KRpep-2d inhibits the enzyme activity of K-Ras(G12D) with an IC50 of 1.6 nM, and with selectivity against wild-type (WT) K-Ras and the K-Ras(G12C) mutant in both cell-free enzyme and cell based assays. Mutated Ras proteins play important roles in cell differentiation, proliferation, and survival of various cancers, and K-Ras(G12D) is considered a very important target as K-Ras mutations underlie 86% of Ras-linked cancers, with 83% of K-Ras mutations being at the G12 residue. KRpep-2d can suppress ERK phosphorylation downstream of K-Ras(G12D) and reduce proliferation in A427 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

• Niida et al (2017) Investigation of the structural requirements of K-Ras(G12D) selective inhibitory peptide KRpep-2d using alanine scans and cysteine bridging. Bioorg Med Chem Lett. 27(12) 2757 PMID: 28457754
• Sakamoto et al (2017) K-Ras(G12D)-selective inhibitory peptides generated by random peptide T7 phage display technology. Biochem Biophys Res Commun. 484(3) 605 PMID: 28153726
• Lim et al (2021) Discovery of cell active macrocyclic peptides with on-target inhibition of KRAS signaling. Chem Sci. 12(48) 15975 PMID: 35024121

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.