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Chemotactic Properties (chemotactic + property)
Selected AbstractsChemotactic activity of oligopeptides containing an EWS motif on Tetrahymena pyriformis: the effect of amidation of the C-terminal residueCELL BIOCHEMISTRY AND FUNCTION, Issue 2 2003László Köhidai Abstract Chemotactic properties of 3,7-mer peptides containing an EWS motive and their peptide amides synthesized and characterized by us were investigated in Tetrahymena pyriformis GL model. Analysis of the peptide acids shows that SEWS possesses exceptionally strong (660%±21; 430%±18) chemoattractant ability at 10,12 and 10,11m respectively. The shorter peptide (EWS) possesses chemorepellent activity, while longer peptides display neutral (WSEWS) or moderate chemoattractant (EWSEWS and GEWSEWS) chemotactic ability. Amidation of the C-terminus can significantly modify the character of peptides: it points to the conclusion that a free ,-COOH group at this position is required for the high efficiency of SEWS, while in the shorter (EWS) and longer peptides (WSEWS and EWSEWS) amidation can result in chemoattractant ligands. Evaluation of the structure,function relationship of these compounds establishes the significance of Glu (E) with its high surface-exposed area and negatively-charged side chain. The high discriminative ability and good chemotactic responsiveness of Tetrahymena support the theory that a chemotactic signalling mechanism working in higher levels of phylogeny is a well conserved and inducible one even in protozoa. Copyright © 2002 John Wiley & Sons, Ltd. [source] Role for cAMP-protein kinase A signalling in augmented neutrophil adhesion and chemotaxis in sickle cell diseaseEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2007Andreia A. Canalli Abstract The significance of the leukocyte in sickle cell disease (SCD) pathophysiology is becoming increasingly recognised; we sought to examine whether the chemotactic properties of neutrophils of SCD individuals may be altered and, further, to better understand the signalling events that mediate altered SCD neutrophil function. Adhesion to immobilised fibronectin (FN) and chemotaxis of control and SCD neutrophils were assessed using in vitro static adhesion assays and 96-well chemotaxis chamber assays. Adhesion assays confirmed a significantly higher basal adhesion of SCD neutrophils to FN, compared with control neutrophils. Chemotaxis assays established, for the first time, that SCD neutrophils demonstrate greater spontaneous migration and, also, augmented migration in response to IL-8, when compared with control neutrophils. Co-incubation of SCD neutrophils with KT5720 (an inhibitor of PKA) abrogated increased basal SCD neutrophil adhesion, spontaneous chemotaxis and IL-8-stimulated chemotaxis. Stimulation of SCD neutrophils with IL-8 also significantly augmented SCD neutrophil adhesion to FN with a concomitant increase in cAMP levels and this increase in adhesion was abolished by KT5720. Interestingly, the adhesive properties of neutrophils from SCD individuals on hydroxyurea therapy were not significantly altered and results indicate that a reduction in intracellular cAMP may contribute to lower the adhesive properties of these cells. Data indicate that up-regulated cAMP signalling plays a significant role in the altered adhesive and migratory properties in SCD neutrophils. Such alterations may have important implications for the pathophysiology of the disease and the cAMP-PKA pathway may represent a therapeutic target for the abrogation of altered leukocyte function. [source] Synthesis of oligotuftsin-based branched oligopeptide conjugates for chemotactic drug targetingJOURNAL OF PEPTIDE SCIENCE, Issue 5 2006Gábor Mezö Abstract The synthesis and chemotactic properties of a new class of branched oligopeptide-based conjugates are described. Tetratuftsin derivatives containing chemotactic formyl tripeptides (For-MLF, For-NleLF or For-MMM) in branches were prepared by stepwise solid-phase peptide synthesis. The influence of the composition and ionic charge of the carrier-branched oligopeptide on the chemotactic behaviour of the conjugate was studied in Tetrahymena pyriformis. Conjugates with methotrexate (Mtx) as a drug component was also prepared. For this, a GFLGC spacer, cleavable by cathepsin B, was used. The spacer with N -terminal methotrexate was coupled to the chloroacetylated chemotactic carrier molecule by thioether bond formation. The chemotactic activity and cytotoxity of Mtx conjugates were also studied. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd. [source] Synthesis of oligopeptides with the sequence SXWS and their chemotactic effects on a ciliated protozoan Tetrahymena pyriformis,JOURNAL OF PEPTIDE SCIENCE, Issue 1 2002Eszter Illyés Abstract In this paper, the solid phase synthesis and chemical characterization of members of an SXWS sub-library (SAWS, SDWS and SKWS) as well as the comparison of their chemotactic properties with those of SEWS, which exhibits a prominent effect at 10,12M on a ciliated protozoan, Tetrahymena pyriformis, are described. We found that the chemotaxis of cells induced with the SXWS peptides varied according to the nature of the amino acid residue (Ala, Asp, Lys) in position X. The chemotactic activity of SEWS was not surpassed by any of three new tetrapeptides, although SAWS was also chemoattractant. Interestingly, SDWS, with an acidic side chain at position X, could not elicit any chemotactic response. SKWS, however, showed mild but significant chemorepellent activity over a wide concentration range. Chemotactic selection studies showed that the two chemoattractant peptides (SAWS and SEWS) had an expressed ability to select high-responder offspring cell populations. Peptides with neutral (SDWS) or chemorepellent (SKWS) properties were not able to select such subpopulations from the mixed cultures of Tetrahymena, indicating that the chemotactic response elicited by SXWS peptides is ligand-specific. For ligand-binding experiments N -terminally labelled fluorescent derivatives of SXWS peptides were prepared, applying [4-[7-hydroxycoumaryl]]acetic acid (Hca -OH) or 4-ethoxymethylene-2-[1]-naphthyl-5(4H)-oxazolone (naOx -OEt) as markers. Hca -OH was introduced using an active ester technique as the last step of SPPS, or after cleavage in solution. The oxazolone naOx -OEt reacted with the amino group of the peptide by liberation of EtOH. The binding characteristics of fixed Tetrahymena cells with the naOx -labelled peptides showed good correlation between binding profiles and chemotactic responsiveness (SEWS > SAWS > SDWS , SKWS). A similar binding pattern was observed in the case of Hca -peptides (SEWS > SAWS > SDWS). Hca -SKWS, however, bound remarkably to the cell surface. The binding activity of the Hca -peptides was less pronounced than that of the naOx -peptides, indicating the importance of the fluorophores applied. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd. [source] Studies on the conformational properties of CP-1042,55, the hinge region of CP-10, using circular dichroism and RP-HPLCCHEMICAL BIOLOGY & DRUG DESIGN, Issue 6 2000E. Lazoura Abstract: The conformational properties of CP-1042,55, a peptide corresponding to the hinge region of CP-10, were investigated using circular dichroism spectroscopy and reverse-phase high-performance liquid chromatography (RP-HPLC). The circular dichroism studies indicated that CP-1042,55 formed considerable secondary structure in the presence of hydrophobic solution environments including 50% acetonitrile, 50% trifluoroethanol and 200 mm sodium dodecyl sulfate, which comprised a mixture of ,-helix and ,-sheet. The effect of temperature on the conformation of CP-1042,55 was investigated between 5 and 40°C, with very small changes in the spectra being observed.RP-HPLC was then used to investigate the effect of temperature on the conformation of CP-1042,55 in the presence of a hydrophobic surface. Using a C18 -adsorbent, CP-1042,55 exhibited a conformational transition at 25°C, which was associated with an increase in the chromatographic contact area and the binding affinity of the peptide for the stationary phase. In addition, near-planar bandbroadening behaviour indicated that conformational species interconverted with rapid rate constants compared with the chromatographic time scale. These results indicated that the conformational change at 25°C in theRP-HPLC system most likely corresponds to the unfolding of an ,-helical and/or ,-sheet structure to an extended coil structure. Therefore, the strong chemotactic properties of this peptide may be attributed to its ability to form considerable secondary structure in the presence of a hydrophobic environment. [source] | ||||||||||