Selectivity in the mechanism of action of antimicrobial mastoparan peptide Polybia-MP1

Many potent antimicrobial peptides also present hemolytic activity, an undesired collateral effect for the therapeutic application. Unlike other mastoparan peptides, Polybia-MP1 (IDWKKLLDAAKQIL), obtained from the venom of the social wasp Polybia paulista, is highly selective of bacterial cells. The study of its mechanism of action demonstrated that it permeates vesicles at a greater rate of leakage on the anionic over the zwitterionic, impaired by the presence of cholesterol or cardiolipin; its lytic activity is characterized by a threshold peptide to lipid molar ratio that depends on the phospholipid composition of the vesicles. At these particular threshold concentrations, the apparent average pore number is distinctive between anionic and zwitterionic vesicles, suggesting that pores are similarly formed depending on the ionic character of the bilayer. To prospect the molecular reasons for the strengthened selectivity in Polybia-MP1 and its absence in Mastoparan-X, MD simulations were carried out. Both peptides presented amphipathic alpha-helical structures, as previously observed in Circular Dichroism spectra, with important differences in the extension and stability of the helix; their backbone solvation analysis also indicate a different profile, suggesting that the selectivity of Polybia-MP1 is a consequence of the distribution of the charged and polar residues along the peptide helix, and on how the solvent molecules orient themselves according to these electrostatic interactions. We suggest that the lack of hemolytic activity of Polybia-MP1 is due to the presence and position of Asp residues that enable the equilibrium of electrostatic interactions and favor the preference for the more hydrophilic environment.

Reaction microtextures of monazite: Correlation between chemical and age domains in the Nazare Paulista migmatite, SE Brazil

Back-scattered imaging, X-ray element mapping and electron microprobe analyzer (EMPA) chemical dating reveal complex compositional and age zoning in monazite crystals from different layers and textural positions in a garnet-bearing migmatite in SE Brazil. Y-rich (variable Y(2)O(3), averaging 2.5 wt.%) relict cores are preserved in mesosome and melanosome monazite, and correspond to 793 +/- 6 Ma inherited crystals possibly generated in a previous metamorphic event. These cores are overgrown and widely replaced by two generations of monazite, which are present in all migmatite layers. The first, also Y-rich (average 2.5 wt.% Y(2)O(3)), was produced at similar to 635 Ma during prograde metamorphism under subsolidus conditions, while the second has an Y-poor (<1.5 wt.% Y(2)O(3)), low Th/U signature, and precipitated from low Y and HREE anatectic melts produced by reactions in which garnet was inert. Quartz-rich trondhjemitic leucosome represents lower temperature melt (bearing some subsolidus quartz and garnet with included monazite) formed at temperatures below muscovite breakdown; its Y-poor monazite indicates an age of 617 +/- 6 Ma. Granitic leucosomes formed close to peak metamorphic conditions (T>750 degrees C) above muscovite breakdown have their slightly younger character confirmed by a 609 +/- 7 Ma low-Y monazite age. A similar 606 +/- 5 Ma age was obtained for low-Y monazite rims and domains in mesosome and melanosome, and reflects the time of monazite saturation in interstitial granitic melt that was trapped in these layers. Our results confirm that inherited monazite crystals can be preserved during partial melting at temperatures above muscovite breakdown. Moreover, careful textural control aided by X-ray chemical mapping may allow monazite generated at different stages in a similar to 25 Myr prograde metamorphic path to be identified and dated using an electron microprobe. (C) 2008 Elsevier B.V. All rights reserved.