Differential Stability of Aurein 1.2 Pores in Model Membranes of Two Probiotic Strains

Aurein 1.2 is an antimicrobial peptide from the skin secretion of an Australian frog. In the previous experimental work, we reported a differential action of aurein 1.2 on two probiotic strains Lactobacillus delbrueckii subsp. bulgaricus (CIDCA 331) and Lactobacillus delbrueckii subsp. lactis (CIDCA 133). The differences found were attributed to the bilayer compositions. Cell cultures and CIDCA 331-derived liposomes showed higher susceptibility than the ones derived from the CIDCA 133 strain, leading to content leakage and structural disruption. Here, we used molecular dynamics simulations to explore these systems at the atomistic level. We hypothesize that if the antimicrobial peptides organized themselves to form a pore, it will be more stable in membranes that emulate the CIDCA 331 strain than in those of the CIDCA 133 strain. To test this hypothesis, we simulated preassembled aurein 1.2 pores embedded into bilayer models that emulate the two probiotic strains. It was found that the general behavior of the systems depends on the composition of the membrane rather than the preassemble system characteristics. Overall, it was observed that aurein 1.2 pores are more stable in the CIDCA 331 model membranes. This fact coincides with the high susceptibility of this strain against antimicrobial peptide. In contrast, in the case of the CIDCA 133 model membranes, peptides migrate to the water-lipid interphase, the pore shrinks, and the transport of water through the pore is reduced. The tendency of glycolipids to make hydrogen bonds with peptides destabilizes the pore structures. This feature is observed to a lesser extent in CIDCA 331 due to the presence of anionic lipids. Glycolipid transverse diffusion (flip-flop) between monolayers occurs in the pore surface region in all the cases considered. These findings expand our understanding of the antimicrobial peptide resistance properties of probiotic strains.Fil: Balatti, Galo Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Domene, Carmen. University of Bath; Reino UnidoFil: Martini, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Pickholz, Mónica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentin

Electronic structure of nitrogen-carbon alloys (a-CNx) determined by photoelectron spectroscopy

The electronic structure of nitrogen-containing diamondlike films prepared by sputtering was determined by photoelectron spectroscopy. The N 1s core-level spectra are constituted by two peaks at 400.5 and 398.2 eV associated with substitutional N sp(2) in aromatic rings and N bonded to C sp(3), respectively. On increasing N, the top of the valence band suffers profound changes. The new features are identified by a comparison of the experimental spectra with theoretically calculated density of states of nitrogen-containing graphite and C3N4 structures. [S0163-1829(98)04004-1].5742536254

Low-temperature structural model of hcp solid C70_{70}

We report intermolecular potential-energy calculations for solid C_${70}$ and determine the optimum static orientations of the molecules at low temperature; we find them to be consistent with the monoclinic structural model proposed by us in an earlier report [Solid State Commun. {\bf 105), 247 (1998)]. This model indicates that the C_5 axis of the molecule is tilted by an angle $\approx$18^o from the monoclinic b axis in contrast with the molecular orientation proposed by Verheijen {\it et al.} [J. Chem. Phys. {\bf 166}, 287 (1992)] where the C_5 axis is parallel to the monoclinic b axis. In this calculation we have incorporated the effective bond charge Coulomb potential together with the Lennard-Jones potential between the molecule at the origin of the monoclinic unit cell and its six nearest neighbours, three above and three below. The minimum energy configuration for the molecular orientations turns out to be at $\theta$=18^o, $\phi$=8^o, and $\psi$=5^o, where $\theta$, $\phi$, and $\psi$ define the molecular orientations.Comment: ReVTeX (4 pages) + 2 PostScript figure

A global review on short peptides: frontiers and perspectives

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide “drugs” initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed

Understanding Conformational Dynamics of Complex Lipid Mixtures Relevant to Biology

This is a perspective article entitled “Frontiers in computational biophysics: understanding conformational dynamics of complex lipid mixtures relevant to biology” which is following a CECAM meeting with the same name.Fil: Friedman, Ran. Linnæus University; ArgentinaFil: Khalid, Syma. University of Southampton; Reino UnidoFil: Aponte Santamaría, Camilo. Ruprecht-Karls-Universität Heidelberg; Alemania. Universidad de los Andes; ColombiaFil: Arutyunova, Elena. University of Alberta; CanadáFil: Becker, Marlon. Westfälische Wilhelms Universität; AlemaniaFil: Boyd, Kevin J.. University of Connecticut; Estados UnidosFil: Christensen, Mikkel. University Aarhus; DinamarcaFil: Coimbra, João T. S.. Universidad de Porto; PortugalFil: Concilio, Simona. Universita di Salerno; ItaliaFil: Daday, Csaba. Heidelberg Institute for Theoretical Studies; AlemaniaFil: Eerden, Floris J. van. University of Groningen; Países BajosFil: Fernandes, Pedro A.. Universidad de Porto; PortugalFil: Gräter, Frauke. Heidelberg University; Alemania. Heidelberg Institute for Theoretical Studies; AlemaniaFil: Hakobyan, Davit. Westfälische Wilhelms Universität; AlemaniaFil: Heuer, Andreas. Westfälische Wilhelms Universität; AlemaniaFil: Karathanou, Konstantina. Freie Universität Berlin; AlemaniaFil: Keller, Fabian. Westfälische Wilhelms Universität; AlemaniaFil: Lemieux, M. Joanne. University of Alberta; CanadáFil: Marrink, Siewert J.. University of Groningen; Países BajosFil: May, Eric R.. University of Connecticut; Estados UnidosFil: Mazumdar, Antara. University of Groningen; Países BajosFil: Naftalin, Richard. Colegio Universitario de Londres; Reino UnidoFil: Pickholz, Mónica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Piotto, Stefano. Universita di Salerno; ItaliaFil: Pohl, Peter. Johannes Kepler University; AustriaFil: Quinn, Peter. Colegio Universitario de Londres; Reino UnidoFil: Ramos, Maria J.. Universidad de Porto; PortugalFil: Schiøtt, Birgit. University Aarhus; DinamarcaFil: Sengupta, Durba. National Chemical Laboratory India; IndiaFil: Sessa, Lucia. Universita di Salerno; ItaliaFil: Vanni, Stefano. University Of Fribourg;Fil: Zeppelin, Talia. University Aarhus; DinamarcaFil: Zoni, Valeria. University of Fribourg; SuizaFil: Bondar, Ana-Nicoleta. Freie Universität Berlin; AlemaniaFil: Domene, Carmen. University of Oxford; Reino Unido. University of Bath; Reino Unid

Accumulation of an Antidepressant in Vesiculogenic Membranes of Yeast Cells Triggers Autophagy

Many antidepressants are cationic amphipaths, which spontaneously accumulate in natural or reconstituted membranes in the absence of their specific protein targets. However, the clinical relevance of cellular membrane accumulation by antidepressants in the human brain is unknown and hotly debated. Here we take a novel, evolutionarily informed approach to studying the effects of the selective-serotonin reuptake inhibitor sertraline/Zoloft® on cell physiology in the model eukaryote Saccharomyces cerevisiae (budding yeast), which lacks a serotonin transporter entirely. We biochemically and pharmacologically characterized cellular uptake and subcellular distribution of radiolabeled sertraline, and in parallel performed a quantitative ultrastructural analysis of organellar membrane homeostasis in untreated vs. sertraline-treated cells. These experiments have revealed that sertraline enters yeast cells and then reshapes vesiculogenic membranes by a complex process. Internalization of the neutral species proceeds by simple diffusion, is accelerated by proton motive forces generated by the vacuolar H+-ATPase, but is counteracted by energy-dependent xenobiotic efflux pumps. At equilibrium, a small fraction (10–15%) of reprotonated sertraline is soluble while the bulk (90–85%) partitions into organellar membranes by adsorption to interfacial anionic sites or by intercalation into the hydrophobic phase of the bilayer. Asymmetric accumulation of sertraline in vesiculogenic membranes leads to local membrane curvature stresses that trigger an adaptive autophagic response. In mutants with altered clathrin function, this adaptive response is associated with increased lipid droplet formation. Our data not only support the notion of a serotonin transporter-independent component of antidepressant function, but also enable a conceptual framework for characterizing the physiological states associated with chronic but not acute antidepressant administration in a model eukaryote

A global review on short peptides: frontiers and perspectives

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide “drugs” initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed

AM1/CI study of a molecular rectifier

Electronic and conformational studies on the push-pull system Z-beta-(1-hexadecyl-4-quinolinium)-gamma-cyano-4-styrldicyanomethanide (C16H33-Q3CNQ) have recently been reported. Based on semi-empirical correlated PM3/ZINDO calculations, the rectifying properties of Langmuir-Blodgett films of these species have been interpreted in terms of a zwitterionic ground state. We present a series of electronic and conformational studies on CH3-Q3CNQ based on semi-empirical calculations to assess solvent, external electric field and correlation effects. The ground state conformation obtained is not of zwitterionic type, and a different interpretation of the intramolecular process of rectification of this system is presented. (C) 1998 Elsevier Science B.V.4322899

Interchain And Correlation Effects In Oligothiophenes

In the present work we present ab initio 3-21 G* calculations on oligothiophene pairs. Electronic correlation has been accounted for at MP2 level. Electronic structures of a series of bithiophene and terthiophene pairs were investigated as function of the intermolecular distance, for neutral and charged systems. The results indicate that the stability of π-dimers increases with the oligomer size and that the intermolecular interaction can be strong enough to allow an intermolecular charge separation.1011528529Hill, M.G., Mann, K.R., Miller, L.L., Penneau, J.F., (1992) J.Am.Chem.Soc., 114, p. 2728SPARTAN, (Wavefunction Inc, 18401 Von Karman Ave, #370, Irvine, CA 92715 USA, © 1995 Wavefunction, Inc.)Schmidt, M.W., (1993) J. Comput. Chem., 14, p. 1347Ehrendorfer, Ch., Karpfen, A., (1994) J.Phys.Chem., 98, p. 7492Yu, Y., Gunic, E., Zinger, B., Miller, L.L., (1996) J.Am.Chem.Soc., 118, p. 101

Theoretical Investigation On π-dimer Formation In Oligothiophenes

The electronic structure and stability of oligothiophene pairs (both neutral and positively charged) up to quaterthiophenes are investigated by ab initio calculations which explicitely taken electron-electron correlation into account. The results indicate that the stability of π-dimers increases with the oligomer size in good agreement with experimental data and that the intermolecular interaction can be strong enough to allow for an intermolecular charge separation. Absorption spectra in the visible to ultra-violet (vis-UV) region, commonly used to characterize charged defects in oligomers and polymers as well as π-dimers, was simulated by a semiempirical technique and the results were found very consistent with the available experimental data of these systems. © 2004 Elsevier B.V. All rights reserved.7171-399106Fichou, (1999) Handbook of Oligo- And Polithiophenes, , Wiley-VCH Weinheim DBrédas, J.L., Street, G.B., (1985) Acc. Chem. Res., 18, p. 309Gao, Y., Liu, C.-G., Jiang, Y.-S., (2002) J. Phys. Chem. a, 106, p. 5380Geskin, V.M., Brédas, J.L., (2003) Chem. Phys. Chem., 4, p. 498Miller, L.L., Mann, K.R., (1996) Acc. Chem. Res., 29, p. 417Roncali, J., (2000) Acc. Chem. Res., 33, p. 147Schwartz, B.J., (2003) Annu. Rev. Phys. Chem., 54, p. 141Jiang, X., (2001) J. Mater. Chem., 11, p. 3043Yu, H., Xu, B., Swager, T., (2003) J. Am. Chem. Soc., 125, p. 1142Nelson, J.C., Saven, J.G., Moore, J.S., Wolynes, P.G., (1997) Science, 277, p. 1793Pickholz, M., Stafström, S., (2001) Chem. Phys., 270, p. 245Van Duijneveldt, F.B., Van Duijneveldt-Vande Rijdt, J.G.C.M., Van Lenthe, J.H., (1994) Chem. Rev., 94, p. 1873Frisch, (2003) Gaussian 03 Revision A.1, , Gaussian Pittsburgh, PA M.JSchmidt, M.W., (1993) J. Comput. Chem., 14, p. 1347(1995) SPARTAN, , (Wavefunction Inc., Irvine CA USA)Nishinaga, T., Wakamiya, A., Yamazaki, D., Komatsu, K., (2004) J. Am. Chem. Soc., 126, p. 3163Bak, B., Christensen, D., Hansen-Nygaard, L., Rastrup-Andersen, J., (1961) J. Mol. Spectrosc., 7, p. 58Irle, S., Lischka, H., (1995) J. Chem. Phys., 103, p. 22Prosa, T.J., Winokur, M.J., Moulton, J., Smith, P., Heeger, A.J., (1992) Macromolecules, 25, p. 4364Lovinger, A.J., (1998) Chem. Mater., 10, p. 3275Becke, A.D., (1993) J. Chem. Phys., 98, p. 5648Cao, J., Curtis, M.D., (2003) Chem. Mater., 15, p. 4424Jackson, J.D., (1998) Classical Electrodynamics, , 3rd ed. Wiley New YorkHill, M.G., Mann, K.R., Miller, L.L., Penneau, J.F., (1992) J. Am. Chem. Soc., 114, p. 2728Hapiot, P., Audebert, P., Monnier, K., Pernaut, J.-M., Garcia, P., (1994) Chem. Mater., 6, p. 1549Bauerle, P., Segelbacher, U., Maier, A., Mehring, M., (1993) J. Am. Chem. Soc., 115, p. 10217Horowitz, G., Yassar, A., Von Bardeleben, H.J., (1994) Synth. Metals., 62, p. 245Bidan, G., De Nicola, A., Enée, V., Guillerez, S., (1998) Chem. Mater., 10, p. 1052Raimundo, J.M., Levillain, E., Gallego-Planas, N., Roncali, J., (2000) Electrochem. Commun., 2, p. 211Sirringhaus, H., (1999) Nature, 401, p. 68