D4-2 (SIRPa inhibitor) peptide

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

Batch to batch variation of the purity

D4-2 is a 15-residue thioether-macrocyclic peptide that acts as a noncompetitive, allosteric inhibitor of the CD47–SIRPα interaction and potentiates antibody-dependent cellular phagocytosis of tumour cells.

Identified by the RaPID system, it contains the N-terminal chloroacetyl group cyclized onto Cys14 and a conserved R(F/Y)(S/T)(A/P)V motif. D4-2 binds the IgV domain of mouse SIRPα with 1:1 stoichiometry and K_D values of ~10 nM (C57BL/6) and 8.22 nM (NOD). A 1.36 Å crystal structure shows a 976.5 Ų interface in which 10 of the 15 residues contact SIRPα, forming an intermolecular antiparallel β-sheet with the C′ and E strands plus 22 hydrogen bonds and 4 salt bridges; A5 and P11 fill hydrophobic pockets at F51 and F56. Binding outside the CD47 site reshapes the C′E loop and lowers the intrinsic affinity of SIRPα for CD47. D4-2 is highly selective for mouse SIRPα over mouse SIRPβ and human SIRPα, and enhances the antitumour activity of rituximab in vivo.

• Hazama D, Yin Y, Murata Y, et al. Macrocyclic Peptide-Mediated Blockade of the CD47-SIRPα Interaction as a Potential Cancer Immunotherapy. Cell Chem Biol. 2020;27(9):1181-1191.e7. doi:10.1016/j.chembiol.2020.06.008
• Rodriguez PL, Harada T, Christian DA, Pantano DA, Tsai RK, Discher DE. Minimal "Self" peptides that inhibit phagocytic clearance and enhance delivery of nanoparticles. Science. 2013;339(6122):971-975. doi:10.1126/science.1229568

Trifluoroacetic acid (TFA) is a common counterion from the purification process using High-Performance Liquid Chromatography (HPLC). The presence of TFA can affect the peptide's net weight, appearance, and solubility.

Impact on Net Weight: The TFA salt contributes to the total mass of the product. In most cases, the peptide content constitutes >80% of the total weight, with TFA accounting for the remainder.

Solubility: TFA salts generally enhance the solubility of peptides in aqueous solutions.

In Biological Assays: For most standard in vitro assays, the residual TFA levels do not cause interference. However, for highly sensitive cellular or biochemical studies, please be aware of its presence.