The importance of the methionine configuration in for-Met-Leu-Phe-OMe biological activities.

for-D-Met-L-Leu-L-Phe-OMe was synthesized in order to understand the importance of the methionine configuration on human neutrophil biological activity. Our results show that both chemotactic response and lysozyme release are lower than those of the parent fMLP-OMe, indicating that the specific receptor pocket possesses a well-located, restricted positive area that does not completely face the D-Met residue. The triggering of superoxide anion production does not seem to be sensitive to this variation of the configuration

Differences arising in human neutrophil activation passing from N-formyl to N-acetyl-oligopeptides.

N-formyl- and N-acetyl-peptides were synthesized and compared in order to understand which features can best elicit biological responses. The behavior of N-formyl-peptides confirms the previously found sequential obligations in the residues, while acetyl-derivatives do not seem suitable for an efficacious stimulation of human neutrophils

An exhaustive insight into the pocket charge features of the methionine receptor using fMLP analogs.

Neutrophils play a key role as primary phagocytic cells, because they constitute the first line of defense against bacterial invasion, and contribute to inflammatory processes. the goal of the study herein reported is to clarify the features peculiar to the methionine receptor pocket. it has widley accepted that the L-Met residue seems to induce optimum chemotactic as well as secretory activities. the synthesised analogs, here reported, have clarified that the positively charged area in the Met pocket is i) narrow in dimension, ii) located at well defined distance from the backbone, and iii) oriented in a specific position, not completely surrounding the internally located said chain

Synthesis and biological activity of D-glucopyranosyl peptide T derivatives.

The solid phase procedure, based on the Fmoc (9-fluorenylmethyloxycarbonyl) chemistry, was used to prepare some peptide T analogues in which D-glucopyranosyl units are beta-O-glycosidically linked to Thr4 and/or Thr5 side chains. All glycopeptides showed significant human monocyte chemotaxis and high resistance to degradation by plasma or brain enzymes

Triggering of neutrophil cytotoxicity against an antibody-coated tumour target by TPA

The human erythroid myeloid leukaemia cell line K562 was used as target for human neutrophil cytotoxicity. Neutrophils demonstrated cytotoxicity against K562 only in the presence of a second stimulus, tetradecanoyl phorbol acetate (TPA), a result consistent with previous observations. We now demonstrate that antibody-coated K562 (using OKT9 and 345 monoclonal antibodies) are similarly only sensitive to neutrophils when TPA is added. The presence of both antibody and TPA in the cytotoxic assay resulted in significantly higher levels of cytotoxicity than in the absence of antibody; the result being consistent with a synergistic action between protein kinase C activation and Fc receptor perturbation in the neutrophil. The cytotoxicity against non-coated and antibody-coated targets was markedly inhibited, particularly against the former, by the protein kinase C inhibitor, 1-(5-isoquinoline-sulfonyl)-2-methyl piperazine (H-7). There were marked differences in the extracellular calcium dependency of the two types of cytotoxicity reactions. TPA-activated respiratory burst was unaffected by the presence of non-coated and OKT9-coated targets, whereas TPA-induced lysosomal enzyme release was significantly increased by non-coated targets and a further increase occurred in the presence of OKT9-coated K562

Protein kinase C mediates human neutrophil cytotoxicity

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