Spectroscopic characterization and in vitro studies of biological activity of bradykinin derivatives

Abstract

Eleven multiple analogs of bradykinin—a peptide that is a natural ligand of B1 and B2 receptors but does not bind or activate the B1 receptor unless Arg9 is removed from the sequence by the action of carboxypeptidase N—were synthesized. Their biological activity was examined on T-REx cell lines expressing B1 or B2 receptors using the intracellular IP1 assay. The mRNA expression of B1R and B2R in the lysate of tumor cell lines, e.g., U87-MG (human astrocytoma), SHP-77 (human small cell lung cancer), and H4 (human brain glioma), was determined. For five B1R antagonists, adsorption at the liquid/solid interface (Au nanoparticles (AuNPs) served as the solid surface) was discussed in terms of the vibrations of molecular fragments (structural factors) responsible for the biological properties of these analogs.

Bradykinin and Neurotensin Analogues as Potential Compounds in Colon Cancer Therapy

“…These results are very promising, although they partially diverge from the previous antagonistic tests of our analogues. Our study confirms that BK analogues affect the inhibition and growth of colon cancer cells similarly to studies with glioma and lung cancer cells [30].…”

“…It has been demonstrated that analogues containing pipecolinic acid with the L-configuration (identical to the native protein amino acid configuration) possess stronger antagonistic activity than with the D-configuration [24,62]. Both of these peptides have also been tested against U87-MG human glioblastoma cells or human lung carcinoma cells and also inhibit the growth of the cancer cell lines, mostly by the B1R receptor [30,63,64]. It is well known that this type of receptor plays an important role in tumour growth, and thus the B1R receptor seems to be a good therapeutic target for novel compounds [65,66].…”

“…Peptides were synthesized via the solid-phase method using the Fmoc/tBu strategy as previously described [30] with minor modifications. Briefly, Fmoc-Arg-Wang Resin (GL Biochem, Shanghai, China) was used.…”

“…For example, acylation of the N-terminus suppresses antagonistic activity [26], yet substitution using a bulky group such as 1-adamantaneacetic acid (Aaa) resulted in a significant increase in B2 antagonistic activity in the rat blood pressure test [27,28]. Substitution of the L-proline residue at position 7 (Pro7) with D-phenylalanine ([D-Phe7]) BK is the key structural change in the sequence of BK that alters the steric position of the C-terminal dipeptide Phe8-Arg9 and leads to antagonistic B2R activity [29,30].…”

Plant-Assisted Green Synthesis of MgO Nanoparticles as a Sustainable Material for Bone Regeneration: Spectroscopic Properties

“…Surface-enhanced Raman scattering (SERS) is a highly sensitive, selective, and relatively fast technique that provides information about surface reactions, interfacial charge transfer, and the architecture of the surface-bound molecule-metal complex. It is used for chemical and biological sensing by enhancing the cross-section of Raman scattering from molecules adsorbed on or near the surface of nanostructured materials [61,62]. The enhancement is achieved by plasmon-mediated electric field enhancement or by chemical enhancement [63].…”