Lys-[Des-Arg9]Bradykinin

Product Name:Lys-[Des-Arg9]Bradykinin

CAS No:71800-36-7

Purity:95%

Molar Mass:1032.21

Chemical Formula:C50H73N13O11

Storage:Store at -20 degrees Celsius

Sequence:KRPPGFSPF

Target:bradykinin B1 receptor

Application:Lys-[Des-Arg9]Bradykinin is a synthetic analog of bradykinin, where the C-terminal arginine (Arg9) is removed and an additional lysine is added to the N-terminus. This modification alters its interaction with bradykinin receptors, particularly reducing its affinity for B2 receptors while selectively targeting B1 receptors. Lys-[Des-Arg9]Bradykinin is often used in research to study inflammatory pathways, as B1 receptor activation is associated with chronic inflammation and pain. It is commonly applied in pharmaceutical and biochemical research for investigating the mechanisms of inflammation, vascular permeability, and pain modulation.

Current Research:

Lys-[Des-Arg⁹]-Bradykinin, also known as Lys-des-Arg⁹-BK, is an endogenous kinin peptide that functions as a potent and highly selective agonist for the bradykinin B₁ receptor (B₁R). It is formed through the proteolytic cleavage of bradykinin, specifically by the removal of the C-terminal arginine residue and the addition of an N-terminal lysine. This modification results in a peptide sequence of Lys-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe.

Receptor Specificity and Binding Affinity

Lys-des-Arg⁹-BK exhibits high affinity for the human B₁ receptor, with a reported Kᵢ value of 0.12 nM. In contrast, its affinity for the bradykinin B₂ receptor (B₂R) is significantly lower, with a Kᵢ value exceeding 30,000 nM. This pronounced selectivity underscores its role in mediating B₁R-specific physiological and pathological processes.

Physiological and Pathological Roles

The B₁ receptor is minimally expressed under normal physiological conditions but is upregulated in response to tissue injury, inflammation, and certain diseases. Activation of B₁R by Lys-des-Arg⁹-BK contributes to various inflammatory responses, including vasodilation, increased vascular permeability, and pain sensitization. These effects are particularly relevant in conditions such as chronic inflammation and neuropathic pain.

Research Applications

Due to its specificity and potency as a B₁R agonist, Lys-des-Arg⁹-BK is extensively utilized in research to:

Investigate the role of B₁R in inflammatory and pain pathways.
Evaluate the efficacy of potential B₁R antagonists in preclinical models.
Study the molecular mechanisms underlying B₁R-mediated signal transduction.
Clinical Implications

Given its involvement in mediating inflammatory responses, Lys-des-Arg⁹-BK and the B₁ receptor have become targets of interest in the development of new therapeutic agents aimed at treating inflammatory diseases and pain disorders. Understanding the interactions between Lys-des-Arg⁹-BK and B₁R is crucial for the rational design of such interventions.

Conclusion

Lys-[Des-Arg⁹]-Bradykinin is a key endogenous peptide that selectively activates the bradykinin B₁ receptor, playing a significant role in inflammation and pain modulation. Its specificity makes it a valuable tool in both basic research and the development of targeted therapies for conditions associated with B₁R activation.

Reference:

Farias, N. C., Feres, T., Paiva, A. C., & Paiva, T. B. (2004). Lys-[Leu8, des-Arg9]-bradykinin blocks lipopolysaccharide-induced SHR aorta hyperpolarization by inhibition of Ca++-and ATP-dependent K+ channels. European journal of pharmacology, 498(1-3), 163-169.