72 research outputs found
Synthesis and biological evaluation of new active For-Met-Leu-Phe-OMe analogues containing para-substituted Phe residues. J.Pept.Sci, 18, 418-426, 2012.
No full textIn the present study, we report synthesis and biological evaluation of the N-Boc-protected tripeptides 4a-l and N-For protected tripeptides 5a-l as new For-Met-Leu-Phe-OMe (fMLF-OMe) analogues. All the new ligands are characterized by the C-terminal Phe residue variously substituted at position 4 of the aromatic ring. The agonism of 5a-l and the antagonism of 4a-l (chemotaxis, superoxide anion production, lysozyme release as well as receptor binding affinity) have been examined on human neutrophils. No synthesized compounds has higher activity than the standard fMLF-OMe tripeptide to stimulate chemotaxis, although compounds 5a and 5c with -CH(3) and -C(CH(3))(3), respectively, in position 4 on the aromatic ring, are better than the standard tripeptide to stimulate the production of superoxide anion, in higher concentration. Compounds 4f and 4i, containing -F and -I in position 4, respectively, on the aromatic ring of phenylalanine, exhibit significant chemotactic antagonism. The influence of the different substitution at the position 4 on the aromatic ring of phenylalanine is discussed
Synthesis and activity of chemotactic peptides. Analogues of fMLP-OMe modified at the N-terminal Met residue
No full textResults obtained by studying f-MLP-OMe analogues incorporating proline-methionine chimeras cMtp and tMtp as N-terminal residue, on human neutrophil funtions, have been reporte
Novel chemotactic For-Met-Leu-Phe-OMe (fMLF-OMe) analogues based on Met residue replacement by 4-amino-proline scaffold: Synthesis and bioactivity
No full textcis-(2S,4S) 4-Amino-proline (cAmp) and trans-(2S,4R) 4-amino-proline (tAmp) residues, bearing N-For or
N-Boc substituents at the two amino groups, have been incorporated into the potent chemotactic agent
fMLF-OMe in place of the N-terminal native (S)-methionine to give the analogues 17a–19a and 17b–19b.
The new ligands have been examined for their activity (chemotaxis, superoxide anion production and
lysozyme release) on human neutrophils as agonists and antagonists. Compounds 19a and 19b, bearing
two N-For groups at the proline scaffold, are active and selective chemoattractants. The ligand 18b, containing
N-For at the 4-amino group of the N-Boc-tAmp residue, exhibits significant chemotactic antagonism.
The influence of the different substitution at the N-terminal position of the new analogues is
discussed
Evaluation of 2,3,4,8,13a hexahydro-1H-benzo[5,6]cyclohepta-6,7-dihydroxy[1,2,3-ef][3]benzazepine derivatives as dopamine receptor ligands
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BICYCLIC PEPTIDES - SOLUTION CONFORMATION AND CA-2+ BINDING OF THE HETERODETIC BICYCLIC DECAPEPTIDE CYCLO(GLU1-LEU2-PRO3-GLY4-SER5-ILE6-PRO7-ALA8)-CYCLO(1-GAMMA- 5-BETA) PHE9-GLY10
No full textThe conformational behavior of a heterodetic bicyclic decapeptide (BCPLT) in the absence and in the presence of calcium ions has been studied by means of mono and two-dimensional nmr techniques. Free BCPLT possesses a quite compact structure stabilized by intramolecular bonds and turns. In the structure a cluster of carbonyls is located in a cavity that is supposed to be the cation binding site
Cyclo(His-Pro) exerts anti-inflammatory effects by modulating NF-κB and Nrf2 signalling.
No full textCyclo(His-Pro) is an endogenous cyclic dipeptide that exerts oxidative damage protection by selectively activating the transcription factor Nrf2 signalling pathway. Given the existence of a tight interplay of the Nrf2/NF-κB systems and that the pro-inflammatory response is governed by transcription factor NF-κB, here we sought to investigate whether and how cyclo(His-Pro) interferes with the cross-talk between the antioxidant Nrf2/heme oxygenase-1 and the pro-inflammatory NF-κB pathways. By knocking down the Nrf2 gene, we confirmed that cyclo(His-Pro) inhibits NF-κB nuclear accumulation induced by paraquat in rat pheochromocytoma PC12 cells via the Nrf2/heme oxygenase-1 pathway. The protection required functional heme oxygenase-1 activity, since zinc protoporphyrin IX, a heme oxygenase-1 inhibitor, prevented NF-κB inhibition, and the presence of exogenous carbon monoxide and bilirubin afforded cytoprotection against paraquat-induced toxicity by preventing NF-κB activation. Cyclooxygenase-2 and matrix metalloproteinase 3, two gene products governed by NF-κB, were down-regulated by cyclo(His-Pro) and up-regulated in heme oxygenase-1 knock-down cells. We validated the general mechanism underlying the anti-inflammatory effects by treating PC12 and murine microglial BV2 cells with different pro-inflammatory agents. Finally, cyclo(His-Pro) reduced 12-otetradecanoylphorbol-13-acetate-induced oedema in mouse ear inflammation model. Results, by showing that cyclo(His-pro) suppresses the pro-inflammatory NF-κB signalling via the Nrf2-mediated heme oxygenase-1 activation, contribute to the understanding of essential cellular pathways and allow the proposal of cyclo(His-Pro) as an in vivo anti-inflammatory compound
Synthesis and biological evaluation of the disulfide form of the glutathione analogue gamma-(l-glutamyl)-l-cysteinyl-l-aspartyl-l-cysteine
No full textManuale di chimica farmaceutica. Progettazione, meccanismo d'azione e metabolismo dei farmaci
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