Convergent Synthesis of the Rat Galanin and Study of Its Biological Activity

Russian Journal of Bioorganic Chemistry - The full-length rat galanin (GWTLNSAGYLLGPHAIDNHRSFSDKHGLT-NH2, G29) was prepared by the solid phase peptide synthesis using the Fmoc-strategy. The peptide...     

Chimeric Agonist of Galanin Receptor GALR2 Reduces Heart Damage in Rats with Streptozotocin-Induced Diabetes

Biochemistry (Moscow) - Neuropeptide galanin and its N-terminal fragments reduce the generation of reactive oxygen species and normalize metabolic and antioxidant states of myocardium in...     

Peptide fragments of the fractalkine chemokine domain: Influence on migration of human monocytes

The CX3CL1 Fractalkine is the sole cytokine of the CX3C family. Its molecule consists of an extracellular N-terminal chemokine domain, a mucin-like rod, a transmembrane domain, and an intracellular domain. Fractalkine exhibits the properties of an adhesion molecule in the membrane-bound state. The fractalkine chemokine domain (FCD) is proteolytically released from a cellular membrane in a soluble form. It acts as a chemoattractant for leukocytes which express the CX3CR1 fractalkine receptor. Fractalkine participates in the development of a number of pathological inflammation-mediated processes. Therefore, a search for its inhibitors is an urgent problem. We determined the FCD antigenic determinants and synthesized the corresponding peptides: P41-52 H-Leu-Glu-Thr-Arg-Gln-His-Arg-Leu-Phe-Cys-Ala-Asp-NH₂, P53-60 H-Pro-Lys-Glu-Gln-Trp-Val-Lys-Asp-NH₂, and P60-71 H-Asp-Ala-Met-Gln-His-Leu-Asp-Arg-Gln-Ala-Ala-Ala-NH₂. The biological activity of these peptides was evaluated according to their action on the adhesion and migration of human peripheral blood monocytes which expressed the fractalkine receptor. FCD and the P41-52 peptide significantly increased monocyte adhesion and migration in comparison with the corresponding spontaneous adhesion and migration of the cells. The P53-60 and P60-71 peptides inhibited the FCD-stimulated monocyte adhesion and migration. We analyzed the influence of the prepared peptides on the interaction of FCD with heparin by EIA, because binding of chemokines to glycosaminoglycans of cellular surface and extracellular matrix was one of the conditions of the chemokine migration activity. The P41?C52 peptide competed with FCD for the heparin binding, whereas the P53?C60 and P60?C71 peptides had no significant effect.     

Optimization of the Synthesis of an Apelin-12 Structural Analog and the NMR Study of Its Stability in Human Plasma

Russian Journal of Bioorganic Chemistry - A method for the solid-phase synthesis of the apelin-12 analog has been developed using the Fmoc methodology in combination with the temporary protection...     

Optimal Method for Disulfide Bond Closure in the Synthesis of Atosiban—Antagonist of Oxytocin Receptors

Russian Journal of Bioorganic Chemistry - This work is devoted to the large-scale solid-phase synthesis (SPS) of Atosiban, Mpa1-D-Tyr(OEt)-Ile-Thr-Asn-Cys6-Pro-Orn-Gly-NH2 cyclic 1,6 disulfide, the...     

Optimization of the Solid Phase Synthesis of the Ingramon Peptide Antagonist of the Human Monocyte Chemoattractant Protein 1 (MCP-1)

Russian Journal of Bioorganic Chemistry - The solid phase synthesis (SPS) of the ingramon peptide antagonist of the human monocyte chemoattractant protein-1...     

Inhibitor of inflammation,peptide fragment (65–76) of monocyte chemotactic protein-1 (MCP-1), inhibits binding of MCP-1 to heparin

Monocyte chemotactic protein-1 (MCP-1, CCL2) is one of the most important chemokines involved in inflammation. MCP-1 stimulates migration of monocytes and certain lymphocyte populations to the affected area, in particular to the sites of atherosclerotic plaque formation. Development of drugs inhibiting MCP-1 is now a topical task. We earlier designed and synthesized a dodecapeptide from C-terminal domain of MCP-1 (65–76, peptide X) that possessed an anti-inflammatory activity. The mechanism of action of chemokines (in particular, of MCP-1) in vivo is based on activation of CCR2 receptor on target cells and binding to glycosaminoglycans (GAGs) on the cell surface of and extracellular matrix. Peptide X did not affect the MCP-1-CCR2 interaction. Thus, we hypothesized that peptide X could impair MCP-1 binding to GAGs. Here we studied the effect of peptide X on the MCP-1 binding to heparin using the label-free biosensing device Picoscope®, enzyme-linked immunoassay (ELISA), and the intrinsic fluorescence method. According to the data obtained, peptide X interfered with the MCP-1-heparin binding, which may be due to the competition of peptide X with MCP-1 for heparin binding sites. Probably, this effect determines the anti-inflammatory activity of peptide X in vivo.