PMID- 23880927 OWN - NLM STAT- MEDLINE DCOM- 20140401 LR - 20211021 IS - 1660-3397 (Electronic) IS - 1660-3397 (Linking) VI - 11 IP - 7 DP - 2013 Jul 4 TI - pH-dependent solution structure and activity of a reduced form of the host-defense peptide myticin C (Myt C) from the mussel Mytilus galloprovincialis. PG - 2328-46 LID - 10.3390/md11072328 [doi] AB - Myticin C (Myt C) is a highly variable host-defense peptide (HDP) associated to the immune response in the mediterranean mussel (Mytilus galloprovincialis), which has shown to be active across species due to its strong antiviral activity against a fish rhabdovirus found in fish cells overexpressing this HDP. However, the potential antimicrobial properties of any synthetic analogue of Myt C has not yet been analysed. Thus, in this work we have synthesised the sequence of the mature peptide of Myt C variant c and analysed the structure activity relationships of its reduced (non-oxidized) form (red-MytCc). In contrast to results previously reported for oxidized isoforms of mussel myticins, red-MytCc was not active against bacteria at physiological pH and showed a moderate antiviral activity against the viral haemorrhagic septicaemia (VHS) rhabdovirus. However, its chemotactic properties remained active. Structure/function studies in neutral and acid environments by means of infrared spectroscopy indicated that the structure of red-MytCc is pH dependent, with acid media increasing its alpha-helical content. Furthermore, red-MytCc was able to efficiently aggregate artificial phospholipid membranes at low pH, as well as to inhibit the Escherichia coli growth, suggesting that this activity is attributable to its more structured form in an acidic environment. All together, these results highlight the dynamic and environmentally sensitive behavior of red-Myt C in solution, and provide important insights into Myt C structure/activity relationships and the requirements to exert its antimicrobial/immunomodulatory activities. On the other hand, the pH-dependent direct antimicrobial activity of Myt C suggests that this HDP may be a suitable template for the development of antimicrobial agents that would function selectively in specific pH environments, which are sorely needed in this "antibiotic-resistance era". FAU - Martinez-Lopez, Alicia AU - Martinez-Lopez A AD - Molecular and Cell Institute, University Miguel Hernandez (IBMC-UMH), Elche 03202, Spain. alicia.martinez@umh.es FAU - Encinar, Jose Antonio AU - Encinar JA FAU - Medina-Gali, Regla Maria AU - Medina-Gali RM FAU - Balseiro, Pablo AU - Balseiro P FAU - Garcia-Valtanen, Pablo AU - Garcia-Valtanen P FAU - Figueras, Antonio AU - Figueras A FAU - Novoa, Beatriz AU - Novoa B FAU - Estepa, Amparo AU - Estepa A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130704 PL - Switzerland TA - Mar Drugs JT - Marine drugs JID - 101213729 RN - 0 (Anti-Infective Agents) RN - 0 (Antimicrobial Cationic Peptides) RN - 0 (Antiviral Agents) RN - 0 (Blood Proteins) RN - 0 (Peptides) RN - 0 (Protein Isoforms) RN - 0 (Solutions) RN - 0 (myticin) RN - 0 (polypeptide C) SB - IM MH - Animals MH - Anti-Infective Agents/chemistry/pharmacology MH - Antimicrobial Cationic Peptides/*chemistry/pharmacology MH - Antiviral Agents/chemistry/pharmacology MH - Bivalvia/*chemistry MH - Blood Proteins/*chemistry/pharmacology MH - Cells, Cultured MH - Escherichia coli/drug effects MH - Fishes MH - Hydrogen-Ion Concentration MH - Mytilus/*chemistry MH - Peptides/*chemistry/pharmacology MH - Protein Isoforms/*chemistry/pharmacology MH - Protein Structure, Secondary MH - Rhabdoviridae/drug effects MH - Solutions/*chemistry MH - Structure-Activity Relationship PMC - PMC3736426 EDAT- 2013/07/25 06:00 MHDA- 2014/04/02 06:00 PMCR- 2013/07/01 CRDT- 2013/07/25 06:00 PHST- 2013/04/23 00:00 [received] PHST- 2013/05/30 00:00 [revised] PHST- 2013/06/07 00:00 [accepted] PHST- 2013/07/25 06:00 [entrez] PHST- 2013/07/25 06:00 [pubmed] PHST- 2014/04/02 06:00 [medline] PHST- 2013/07/01 00:00 [pmc-release] AID - md11072328 [pii] AID - marinedrugs-11-02328 [pii] AID - 10.3390/md11072328 [doi] PST - epublish SO - Mar Drugs. 2013 Jul 4;11(7):2328-46. doi: 10.3390/md11072328.