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      • Trichogin GA IV: A versatile template for the synthesis of novel peptaibiotics

        Zotti, Marta De,Biondi, Barbara,Peggion, Cristina,Formaggio, Fernando,Park, Yoonkyung,Hahm, Kyung-Soo,Toniolo, Claudio The Royal Society of Chemistry 2012 Organic & biomolecular chemistry Vol.10 No.6

        <P>Trichogin GA IV, isolated from the fungus <I>Trichoderma longibrachiatum</I>, is the prototype of lipopeptaibols, the sub-class of short-length peptaibiotics exhibiting membrane-modifying properties. This peptaibol is predominantly folded in a mixed 3<SUB>10</SUB>-/α- helical conformation with a clear, albeit modest, amphiphilic character, which is likely to be responsible for its capability to perturb bacterial membranes and to induce cell death. In previous papers, we reported on the interesting biological properties of trichogin GA IV, namely its good activity against Gram positive bacteria, in particular methicillin-resistant <I>S. aureus</I> strains, its stability towards proteolytic degradation, and its low hemolytic activity. Aiming at broadening the antimicrobial activity spectrum by increasing the peptide helical amphiphilicity, in this work we synthesized, by solution and solid-phase methodologies, purified and fully characterized a set of trichogin GA IV analogs in which the four Gly residues at positions 2, 5, 6, 9, lying in the poorly hydrophilic face of the helical structure, are substituted by one (position 2, 5, 6 or 9), two (positions 5 and 6), three (positions 2, 5, and 9), and four (positions 2, 5, 6, and 9) Lys residues. The conformational preferences of the Lys-containing analogs were assessed by FT-IR absorption, CD and 2D-NMR techniques in aqueous, organic, and membrane-mimetic environments. Interestingly, it turns out that the presence of charged residues induces a transition of the helical conformation adopted by the peptaibols (from 3<SUB>10</SUB>- to α-helix) as a function of pH in a reversible process. The role played in the analogs by the markedly increased amphiphilicity was further tested by fluorescence leakage experiments in model membranes, protease resistance, antibacterial and antifungal activities, cytotoxicity, and hemolysis. Taken together, our biological results provide evidence that some of the least substituted among these analogs are good candidates for the development of new membrane-active antimicrobial agents.</P> <P>Graphic Abstract</P><P>One or more Gly-to-Lys replacements on the hydrophilic face of the peptide-template trichogin GA IV modulate its biological properties and promote a pH-mediated, reversible, 3<SUB>10</SUB>- to α-helix transition. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c1ob06178j'> </P>

      • SCISCIESCOPUS

        Trichogin GA IV: an antibacterial and protease-resistant peptide

        De Zotti, Marta,Biondi, Barbara,Formaggio, Fernando,Toniolo, Claudio,Stella, Lorenzo,Park, Yoonkyung,Hahm, Kyung-Soo John Wiley Sons, Ltd. 2009 Journal of Peptide Science Vol.15 No.9

        <P>The antibacterial and hemolytic activities of the amphiphilic helical, membrane-active, lipopeptaibol trichogin GA IV and its [Leu<SUP>11</SUP>-OMe] analogue were compared to those of the partially helical or non-helical 8-meric or 4-meric, C-terminal short sequences, respectively. The study on trichogin GA IV was extended to several methicillin-resistant Staphylococcus aureus strains. Using a large set of enzymes, we also evaluated the resistance to proteolysis of all of the four peptides. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.</P>

      • The Lipid Dependence of Antimicrobial Peptide Activity Is an Unreliable Experimental Test for Different Pore Models

        Bobone, Sara,Roversi, Daniela,Giordano, Lorenzo,De Zotti, Marta,Formaggio, Fernando,Toniolo, Claudio,Park, Yoonkyung,Stella, Lorenzo American Chemical Society 2012 Biochemistry Vol.51 No.51

        <P>Antimicrobial peptides usually kill bacteria by making their membranes permeable. Two main models (barrel-stave and Shai–Matsuzaki–Huang) have been proposed to describe the peptide-induced pores. Although several experimental tests can be exploited to discriminate between these two models, the dependence of peptide activity on lipid properties (intrinsic curvature and membrane thickness) is routinely used for this purpose. Here, we show that, contrary to what is currently accepted, this criterion is unreliable.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bichaw/2012/bichaw.2012.51.issue-51/bi3015086/production/images/medium/bi-2012-015086_0004.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/bi3015086'>ACS Electronic Supporting Info</A></P>

      • KCI등재

        Operative Management of Lumbar Degenerative Disc Disease

        Yu Chao Lee,Mario Giuseppe Tedesco Zotti,Orso Lorenzo Osti 대한척추외과학회 2016 Asian Spine Journal Vol.10 No.4

        Lumbar degenerative disc disease is extremely common. Current evidence supports surgery in carefully selected patients who have failed non-operative treatment and do not exhibit any substantial psychosocial overlay. Fusion surgery employing the correct grafting and stabilization techniques has long-term results demonstrating successful clinical outcomes. However, the best approach for fusion remains debatable. There is some evidence supporting the more complex, technically demanding and higher risk interbody fusion techniques for the younger, active patients or patients with a higher risk of non-union. Lumbar disc arthroplasty and hybrid techniques are still relatively novel procedures despite promising short-term and mid-term outcomes. Long-term studies demonstrating superiority over fusion are required before these techniques may be recommended to replace fusion as the gold standard. Novel stem cell approaches combined with tissue engineering therapies continue to be developed in expectation of improving clinical outcomes. Results with appropriate follow-up are not yet available to indicate if such techniques are safe, cost-effective and reliable in the long-term.

      • KCI등재

        Experimental Study To Develop A Method For Improving Sample Collection To Monitor Laryngoscopes After Reprocessing

        Savina Ditommaso,Monica Giacomuzzi,Elisa Ricciardi,Carla Zotti 대한소화기내시경학회 2018 Clinical Endoscopy Vol.51 No.5

        Background/Aims: The microbiological surveillance of endoscopes and automated flexible endoscope reprocessing have been provento be two of the most diffcult and controversial areas of infection control in endoscopy. The purpose of this study was to standardizea sampling method for assessing the effectiveness of standard reprocessing operating procedures for flexible fiberoptic laryngoscopes(FFLs). Methods: First, the sampling devices were directly inoculated with Bacillus atrophaeus spores; second, tissue non tissue (TNT) wipeswere tested on artificially contaminated surfaces and on FFLs. Results: Comparison of the sponges, cellulose, and TNT wipes indicated that the TNT wipes were more effective in releasing spores (93%)than the sponges (49%) and cellulose wipes (52%). The developed protocol provides a high effciency for both collection and extractionfrom the stainless steel surface (87% of the spores were removed and released) and from the FFL (85% of the spores were removed andreleased), with relatively low standard deviations for recovery effciency, particularly for the analysis of the FFL. Conclusions: TNT wipes are more efficient for sampling surface areas, thereby aiding in the accuracy and reproducibility ofenvironmental surveillance.

      • SCISCIESCOPUS

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