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Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Neuroprotective Effect of Short Collagen-Related Peptides andTheir Ability to Interact with ACE Reveal Structure-ActivitySimilarityStanislav I. Schramm, Tatyana N. Danyukova, Kristina V. Glebova,Igor Yu. Nagayev, Ludmila A. Andreeva, and Nikolay F. MyasoedovLaboratory of Neuropharmacology, Institute of Molecular Genetics, Russian Academy ofSciences, Moscow, 123182, RussiaIntroductionCollagen and other similar proteins, both endogenous and exogenous, are a rich source ofshort peptides mainly consisting of proline, hydroxyproline and glycine residues [1]. It wasfound that a collagen-rich diet or chronic neutrophilic inflammation both lead to a multifoldincrease in the level of such short collagen-related (SCR) peptides in the body [2,3]. Todate, various effects of naturally occurring and synthetic SCR peptides on cardiovascular,nervous, immune and digestive systems in health and disease have been reported [1,3,4].However molecular bases of the effects discovered are not yet fully understood. Also itremains unclear whether activities of SCR peptides are mediated by single or diversemolecular target(s). Therefore it is of great importance to compare structure-activity datafor SCR peptides obtained on different models and objects. We have previously found outthat several SCR peptides are neuroprotective in vivo and in vitro [5,6]. The aim of thisinvestigation is to identify structure-activity relationships of SCR peptides for bothneuroprotective activity in vitro and their susceptibility to interact with bovine angiotensinconvertingenzyme (ACE) as substrates/inhibitors.Results and DiscussionPreviously we have shown that C-terminal amino acid residues in the molecules of SCRpeptides provide their neuroprotective effect in a model of oxidative stress-inducedneuronal death [5]. On the other hand the nature of C-terminal peptide sequence is alsoimportant for ACE since this enzyme is a peptidyl dipeptide hydrolase that removes thecarboxyl terminal dipeptide from certain oligopeptides. A series of peptides with a specificstructure of the C-terminus was chosen for this study. One group consisted of peptides withthe C-terminal sequence Gly-Pro, and another one with Pro-Gly (Table 1).Neuroprotective activity of SCR peptides has been assessed on the basis of their ability toTable 1. Neuroprotective activity of SCR peptides and their susceptibility to ACE hydrolysisPeptideNeuroprotectiveactivity aHydrolysisby ACE b , %PeptideNeuroprotectiveactivity aHydrolysisby ACE b , %Peptides with Gly-Pro C-terminal sequence Peptides with Pro-Gly C-terminal sequenceGP + ND c PG − NDPGP + 80 ± 3 GPG + NDN-acetyl-PGP + 100 ± 0 PGPG − 14 ± 5GPGP + 100 ± 0 GPPG − 18 ± 3LPGP ND 100 ± 0 GPGPG − NDFPGP ND 100 ± 0 PGPGPG − NDRPGP ND 100 ± 0 Other peptidesPGGP + 99 ± 2 PGPL − 13 ± 6PGPGP − NDGPGPGP + NDPGPPGP − 100 ± 0a PC-12 cells were incubated with 1mM H 2 O 2 for 30 min; peptide - 1-100 µM.b Peptide - 100 μM; ACE - 20 nM; 50 mM HEPES pH 7.5;;18h at 30 o C.c ND – not determined.512