In previous papers, we observed that dendrimers of peptide mimotopes of the nicotinic receptor ligand site are strong antidotes against the lethality of the nicotinic receptor ligand alpha-bungarotoxin. Although their in vitro activity is identical to that of dendrimers, the corresponding monomeric peptide mimotopes are not effective in vivo. Because the higher in vivo efficiency of dendrimers could not in this case be related to polyvalent interaction, the stability to blood protease activity of monomeric versus tetrabranched dendrimeric mimotope peptides was compared here by incubating three different mimotopes with human plasma and serum. Unmodified peptides and cleaved sequences were followed by high pressure liquid chromatography and mass spectrometry. Tetrabranched peptides were shown to be much more stable in plasma and also in serum. To assess the notable stability of multimeric peptides, different bioactive neuropeptides, including enkephalins, neurotensin and nociceptin, were synthesized in monomeric and tetrabranched forms and incubated with human plasma and serum and with rat brain membrane extracts. All the tetrabranched neuropeptides fully retained biological activity and generally showed much greater stability to blood and brain protease activity. Some tetrabranched peptides were also resistant to trypsin and chymotrypsin. Our findings provide new insights into the possible therapeutic use of bioactive peptides.
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|Titolo:||Synthetic peptides in the form of dendrimers become resistant to protease activity|
|Rivista:||THE JOURNAL OF BIOLOGICAL CHEMISTRY|
|Citazione:||Bracci, L., Falciani, C., Lelli, B., Lozzi, L., Runci, Y., Pini, A., et al. (2003). Synthetic peptides in the form of dendrimers become resistant to protease activity. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 278(47), 46590-46595.|
|Appare nelle tipologie:||1.1 Articolo in rivista|