cyclo(RLsKDK) peptide

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

Batch to batch variation of the purity

The cyclic peptide cyclo(RLsKDK) is a potent and specific inhibitor of the metalloproteinase ADAM8, which plays a crucial role in various physiological processes. This peptide features a six-amino-acid sequence (Arg-Leu-D-Ser-Lys-Asp-Lys) arranged in a cyclic structure, with the incorporation of a D-serine residue to promote a β-turn conformation, enhancing its structural resemblance to the integrin-binding loop of ADAM8. Cyclo(RLsKDK) exhibits high binding affinity to the disintegrin domain of ADAM8, with an IC₅₀ value of 182 nM, attributed to its optimized secondary structure and resistance to proteolytic degradation due to the presence of D-amino acids.

Structure-activity relationship (SAR) studies have revealed that modifications to the hydroxyl group of D-serine or substitutions of key residues, such as arginine, leucine, and lysine, significantly influence the peptide's inhibitory activity. For instance, replacing D-serine with β-homoserine maintains potency, while removal of the hydroxyl group or introduction of a carboxylic acid moiety reduces activity. Hydrophobic substitutions at the leucine position, such as homoleucine, enhance binding, suggesting interactions with a hydrophobic pocket in the ADAM8 binding site. These findings highlight the importance of specific structural features in cyclo(RLsKDK) for its high-affinity interaction with ADAM8.

• Yim V, Noisier AFM, Hung KY, Bartsch JW, Schlomann U, Brimble MA. Synthesis and biological evaluation of analogues of the potent ADAM8 inhibitor cyclo(RLsKDK) for the treatment of inflammatory diseases and cancer metastasis. Bioorg Med Chem. 2016 Sep 15;24(18):4032-4037. doi: 10.1016/j.bmc.2016.06.042. Epub 2016 Jun 23. PMID: 27407033.

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.