The genome sequence of the rice blast fungus Magnaporthe grisea.

Magnaporthe grisea is the most destructive pathogen of rice worldwide and the principal model organism for elucidating the molecular basis of fungal disease of plants. Here, we report the draft sequence of the M. grisea genome. Analysis of the gene set provides an insight into the adaptations required by a fungus to cause disease. The genome encodes a large and diverse set of secreted proteins, including those defined by unusual carbohydrate-binding domains. This fungus also possesses an expanded family of G-protein-coupled receptors, several new virulence-associated genes and large suites of enzymes involved in secondary metabolism. Consistent with a role in fungal pathogenesis, the expression of several of these genes is upregulated during the early stages of infection-related development. The M. grisea genome has been subject to invasion and proliferation of active transposable elements, reflecting the clonal nature of this fungus imposed by widespread rice cultivation.

Neoglycopeptide dendrimer libraries as a source of lectin binding ligands.

[structure: see text] A 15 625-membered peptide dendrimer combinatorial library was acylated with an alpha-C-fucosyl residue at its four N-termini and screened for binding to fucose-specific lectins. Dendrimer FD2 (Fuc-alpha-CH2CO-Lys-Pro-Leu)4(Lys-Phe-Lys-Ile)2Lys-His-Ile-NH2 was identified as a potent ligand against Ulex europaeus lectin UEA-I (IC50 = 11 microM) and Pseudomonas aeruginosa lectin PA-IIL (IC50 = 0.14 microM).

Dynamical properties of semidilute solutions of hydrogen-bonded supramolecular polymers.

The dynamical properties of semidilute solutions of supramolecular polymers formed from molecular recognition directed association between monomers bearing complementary hydrogen bonding groups were investigated by rheological and dynamic light scattering experiments. The steady-state flow curves showed a shear banding type instability, namely the occurrence of a stress plateau sigma(p) above a critical shear rate .gamma(c) . The values of sigma(p)and .gamma(c) were found to be of the same order of magnitude as those of the elastic plateau modulus and the inverse stress relaxation time, respectively. The above features are in agreement with the theoretical predictions based on the reptation model. Dynamic light scattering experiments showed the presence in the autocorrelation function of the concentration fluctuations of a slow viscoelastic relaxation process that is likely to be of Rouse type.

Double dynamers: molecular and supramolecular double dynamic polymers.

The formation of double dynamers, polymers that are dynamic on both the molecular and supramolecular levels, was achieved in solution and corroborated by electron microscopy; NMR and mass spectrometry studies confirm their double molecular and supramolecular nature.

Contraction/extension molecular motion by protonation/deprotonation induced structural switching of pyridine derived oligoamides.

NMR, mass spectrometry and X-ray diffraction studies show reversible structural interconversion between helical and extended forms of pyridine derived oligoamide molecular strands, by simple protonation/deprotonation.

Evaluating the performance of carboxylate platform fermentations across diverse inocula originating as sediments from extreme environments.

To test the hypothesis that microbial communities from saline and thermal sediment environments are pre-adapted to exhibit superior fermentation performances, 501 saline and thermal samples were collected from a wide geographic range. Each sediment sample was screened as inoculum in a 30-day batch fermentation. Using multivariate statistics, the capacity of each community was assessed to determine its ability to degrade a cellulosic substrate and produce carboxylic acids in the context of the inoculum sediment chemistry. Conductance of soils was positively associated with production of particular acids, but negatively associated with conversion efficiency. In situ sediment temperature and conversion efficiency were consistently positively related. Because inoculum characteristics influence carboxylate platform productivity, optimization of the inoculum is an important and realistic goal.

Glycopeptide dendrimers with high affinity for the fucose-binding lectin LecB from Pseudomonas aeruginosa.

The fucose-specific lectin LecB is implicated in tissue binding and biofilm formation by the opportunistic pathogen Pseudomonas aeruginosa, which causes severe respiratory tract infections mainly in immunocompromised patients or cancer patients undergoing chemotherapy. With a view to developing multivalent LecB inhibitors as novel antibacterial agents, a combinatorial library containing 15 625 tetravalent C-fucosyl peptide dendrimers with the basic structure (CFuc-X(6)X(5)X(4))(4)(LysX(3)X(2)X(1))(2)LysIleHisNH(2) (CFuc=alpha-L-fucosyl acetic acid, X(1-6)=amino acids, Lys=lysine branching) was screened for lectin binding using on-bead binding assays. Ten tetravalent and three octavalent dendrimers derived from the identified sequences were prepared by solid-phase peptide synthesis (SPPS), cleaved from the resin, and purified by preparative HPLC. Relative affinities of these soluble ligands to LecB were determined by an enzyme-linked lectin assay (ELLA). Strong binding was observed for tetravalent and octavalent ligands, with up to 440-fold enhancement in potency over fucose for the octavalent cationic dendrimer 2G3 (CFuc-LysPro)(8)(LysLeuPhe)(4)(LysLysIle)(2)LysHisIleNH(2)). Mono- and divalent controls showed affinities similar to fucose, highlighting the importance of multivalency for binding. Docking studies showed that the C-fucosyl group of the dendrimers can adopt the same binding mode as fucose itself, with the peptide arms protruding from the binding pocket and establishing specific contacts with the lectin.

Inhibition and dispersion of Pseudomonas aeruginosa biofilms by glycopeptide dendrimers targeting the fucose-specific lectin LecB.

The human pathogenic bacterium Pseudomonas aeruginosa produces a fucose-specific lectin, LecB, implicated in tissue attachment and the formation of biofilms. To investigate if LecB inhibition disrupts these processes, high-affinity ligands were obtained by screening two 15,536-member combinatorial libraries of multivalent fucosyl-peptide dendrimers. The most potent LecB-ligands identified were dendrimers FD2 (C-Fuc-LysProLeu)(4)(LysPheLysIle)(2)LysHisIleNH(2) (IC(50) = 0.14 microM by ELLA) and PA8 (OFuc-LysAlaAsp)(4)(LysSerGlyAla)(2)LysHisIleNH(2) (IC(50) = 0.11 microM by ELLA). Dendrimer FD2 led to complete inhibition of P. aeruginosa biofilm formation (IC(50) approximately 10 microM) and induced complete dispersion of established biofilms in the wild-type strain and in several clinical P. aeruginosa isolates. These experiments suggest that LecB inhibition by high-affinity multivalent ligands could represent a therapeutic approach against P. aeruginosa infections by inhibition of biofilm formation and dispersion of established biofilms.

Chirality induction and protonation-induced molecular motions in helical molecular strands.

The long oligopyridinedicarboxamide strand 9, containing 15 heterocyclic rings has been synthesized and its helical structure determined by X-ray crystallography. It was shown that the shorter analogue 6 displays induced circular dichroism and amplification of induced chirality upon dissolution in an optically active solvent, diethyl-L-tartrate. A novel class of helical foldamers was prepared, strands 14-16, based on two oligopyridine carboxamide segments linked through a L-tartaric acid derived spacer. These tartro strands display internal chirality induction as well as chirality amplification. NMR spectroscopy (on 8 and 9) and circular dichroism (on 16) studies show that the oligopyridine carboxamide strands undergo reversible unfolding/folding upon protonation. The protonation-induced unfolding has been confirmed by X-ray crystallographic determination of the molecular structure of the extended protonated heptameric form 8(+). The molecular-scale mechano-chemical motions of the protonation-induced structural switching consist of a change of the length of the molecule, from 6 angstroms (6, coiled form) to 29 angstroms (8(+), uncoiled form) for the heptamer and from 12.5 angstroms (9, coiled form, X-ray structure) to 57 angstroms (9(+), uncoiled form, from modeling) for the pentadecamer. Similar unfolding/folding motional processes take place in the L-tartro strands 15 and 16 upon protonation/deprotonation, with loss of helicity-induced circular dichroism on unfolding as shown for the protonated form 16(+).