Chemotactic tripeptide

Scheme 21 Synthesis of a APhe-Containing Chemotactic Tripeptide Analoguel281...

FORMYL RECEPTOR ANTAGONISTS act at formyl receptors which recognize the chemotactic tripeptide... 

Yessotoxin also potentiated the calcium uptake induced in lymphocytes exposed to maitotoxin, although in this case, the effect was insensitive to SKF 96365 [48]. In the presence of extracellular calcium, but not in its absence, yessotoxin decreased cellular levels of adenosine 3, 5 -cyclic monophosphate, owing to activation of phosphodiesterases [38]. hi isolated mitochondria, yessotoxin opened the permeability transition pore, a voltage-dependent calcium channel, at concentrations between 10 and 10 M. Again, this effect required the presence of calcium in the incubation medium [49]. In the presence of the chemotactic tripeptide A-formyl-Meth-Leu-Phe, yessotoxin increased the motihty of mussel immunocytes, an effect that was again inhibited by verapamil [50]. 

Figure 5 Double-quantum C- C correlation spectra of the solid chemotactic tripeptide formyl-Met-Leu-Phe-OH. Such two-dimensional spectra give signals due to spatially proximal carbons, and thus provide means for determining the conformation of insoluble peptides. Together with other two- and three-dimensional experiments, solid-state NMR structures of proteins are now within reach, as is done routinely in liquid NMR using scalar couplings (a through-bond interaction). (Reproduced with permission from Rienstra C etal. (2000) Journal of the American Chemical Society 22 10979-10990 American Chemical Society.)...

The chemotactic tripeptide fMLP, bacterial lysopoly-saccharide (LPS), complement factor C5a, calcium ionophore, and crosslinking of IgE receptors by... 

There have been quite extensive SAR studies of the structural requirements for agonists and antagonists activity at formyl receptors, mainly within the tripeptide structure, but no non-peptides have been demonstrated to bind selectively. Analogues known to have high chemotactic activity include N-formyl-Met-Ile-Phe-Leu, N-Acetyl-Met-Leu-Phe, IV-formyl-Met-Leu-lle-Phe and simlar analogues. In contrast, some appear to be inhibitors or antagonists see FORMYL RECEPTOR ANTAGONISTS. 

To our knowledge, the only report of the application of DFM and TFM to peptides has been on the effect of these replacements on the chemotactic activity of the tripeptide formyl-Met-Leu-Phe [19]. The methionine residue in this peptide has been shown to be critical to the bioactivity of the peptide, as replacement by other methionine analogues such as ethionine, norleucine,. S -me thy I cysteine,. S -e thy I cysteine or 2-aminoheptanoic acid results in -4-fold to 264-fold decrease in chemotactic activity in human and rabbit neutrophil migration assays [22-24], Interestingly the DFM- and TFM-containing peptides were found to enhance by -10-fold the directed migration responses of human blood neutrophils. Studies of the effects of DFM and TFM on the bioactivity of other peptides would certainly be worthy of further investigation. 

The COOH terminal tripeptide of ECF-A, Gly-Ser-Glu, is only weakly chemotactic but it causes dose-deppgdpgt suppression of eosinophil chemotactic responses to Val-Gly-Ser-Glu. ... 

Although other chemoattractant factors have temporarily taken a back seat to the intense interest in chemokines, they play unique and important roles in host defense. Obviously, small tripeptides such as fMLP derived from bacterial cell walls can potentially serve as an early warning signal that attract phagocytic cells to sites of infection. Comparisons of the attractive potency of fMLP, C5a, and pro-inflammatory chemokines reveal the former to be more potent and to deviate phagocyte migration away from chemokines (Campbell et al., 1996). It should be noted that a number of formylated peptides like fMLF are chemotactic, but fMLP has been studied most intensively as a prototype (Schiffmann et al., 1978). Two receptors, one with high and the other with lower affinity for fMLP, have recently been cloned. 

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