Eine neue Familie von Lipoglycopeptid-Antibiotika mit einzigartigen strukturellen Merkmalen und ausgeprägter Aktivität gegen Gram-positive Bakterien wird von Stanislav S. Terekhov, Zakhar O. Shenkarev, Vladimir A. Korshun et al. in ihrem Forschungsartikel auf S. 18842 vorgestellt. Gausemycine sind intrinsisch fluoreszierende Verbindungen mit einem einzigartigen Modus der antibakteriellen Wirkung. Die Analyse des Biosynthese-Genclusters entschlüsselte eine ungewöhnliche Enzymologie, die an der Bildung einer bisher unbekannten nicht-proteinogenen Aminosäure beteiligt ist.

We report a novel family of natural lipoglycopeptides produced by Streptomyces sp. INA-Ac-5812. Two major components of the mixture, named gausemycins A and B, were isolated, and their structures were elucidated. The com-pounds are cyclic peptides with a unique peptide core and several remarkable structural features, including unusual posi-tions of D-amino acids, lack of the Ca2+-binding Asp-X-Asp-Gly (DXDG) motif, tyrosine glycosylation with arabinose, presence of 2-amino-4-hydroxy-4-phenylbutyric acid (Ahpb) and chlorinated kynurenine (ClKyn), N-acylation of the or-nithine side chain. These major components of the peptide antibiotic family have pronounced activity against Gram-positive bacteria. The mechanism of action of gausemycins was explored by a number of methods, showing significant differences compared to glycopeptides and related lipopeptides. Gausemycins exhibit only slight Ca2+-dependence of an-timicrobial activity and induce no pore formation at low concentrations. Moreover, there is no detectable accumulation of cell wall biosynthesis precursors under treatment with gausemycins.

Knotwood, the branch base inside the tree stem, which is undesirable in the processing of wood, constitutes an abundantly available biomass residue that is of no commercial value and remains underutilized. However, knotwood, as a rich source of various bioactive molecules, has significant importance for utilization as a renewable feedstock for the production of high-value chemicals. Knotwood in temperate climate zones has been a subject of extensive chemical studies, and a number of secondary metabolites have been characterized, including lignans, norlignans, flavonoids, stilbenoids, phenolic acids, tannins, diarylheptanoids, terpenoids, sterols, quinones, aromatic compounds, and fatty acids. Chemistry of different parts (bark, heartwood, sapwood, stemwood, wood) other than the knotwood of these tree species has also been published. Several phenolics and diarylheptanoids have been reported. These chemical constituents and their associated bioactivities have been reviewed. The structural proximity of the components of knotwood and other parts of these trees was observed. However, the concentration of the extractives was higher in knotwood than in other parts of the trees. The chemistry of knotwood of subtropical trees except Tectona grandis L.f. has not been investigated. Published information on the chemistry and bioactivities of Azadirachta indica Adr. Juss., Mangifera indica L. and Tectona grandis L.f. as representatives of subtropical trees of great economic significance was also compiled and reviewed. The constituents characterized in different parts of these trees were phenolics, terpenoids, limonoids, steroids, quinones, benzophenones and fatty acids. Based on the structural proximity of the components of knotwood and other parts of temperate trees, it is postulated that the chemical constituents characterized in different parts of tree species from subtropical regions may also occur in their hitherto uninvestigated knotwood. Our observations stimulate further chemical investigations of the knotwood of these woody perennials.

The dalbaheptide antibiotic INA 9301 was isolated from a culture of Amycolatopsis orientalis . By using a combination of mass spectrometry and NMR spectroscopy, INA 9301 was assessed as N,N -dimethylvancomycin. Detailed 13 C NMR characteristics of INA9301 in D 2 O and DMSO- d 6 are presented, together with 2D 1 H- 1 H ROESY and 1 H- 13 C gHMBC data, which confirmed the configurations of the asymmetric centers and spatial conformational shape of the molecule in aqueous solution.

The dalbaheptide antibiotic INA 9301 was isolated from a culture of Amycolatopsis orientalis. By using a combination of mass spectrometry and NMR spectroscopy, INA 9301 was assessed as N,N-dimethylvancomycin. Detailed 13C NMR characteristics of INA9301 in D2O and DMSO- d 6 are presented, together with 2D 1H-1H ROESY and 1H-13C gHMBC data, which confirmed the configurations of the asymmetric centers and spatial conformational shape of the molecule in aqueous solution.

Propyl 4-O-sulfonato- and 4,4'-di-O-sulfonato-3-O-alpha-L-fucopyranosyl-alpha-L-fucopyranosides, which are related to fragments of brown algal fucoidans, have been synthesized. Their spectral (H-1 and C-13 NMR, NOE) and conformational properties have been studied in combination with molecular modeling and compared with the respective non-sulfated propyl fucobioside. Correlations between chemical shifts and conformational properties of these compounds were investigated.

Propyl 4,4',4"-tri-O-sulfated and non-sulfated (1 --> 3)-alpha-L-fucotriosides which are related to fragments of natural fucoidans have been synthesized. Their spectral and conformational properties have been investigated by H-1 and C-13 NMR, NOE and molecular modeling. Molecular mechanics calculations of the tri-O-sulfated compound as a trianion did not give agreement with the experimental NOE values, while the model with the non-dissociated sulfo group on the non-reducing end worked successfully. (1 --> 3)-Fucobioside fragments in both trisaccharides investigated were shown to have the same range of conformations as in previously described propyl (1 --> 3)-alpha-L-fucobiosides, but with the increase of the relative population of the conformer with the spatial proximity of H-1' and H-4 in the case of non-sulfated fucotrioside.

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The effect of a benzoyl group at O-3 on stereoselectivity of glycosylation by 3-O- and 3,4-di-O-benzoylated 2-O-benzyl-L-fucopyranosyl bromides was studied by direct chemical experiments and computational chemistry. The influence of a benzoyl group at O-3 of the fucosyl donors was shown to have a larger effect on the efficiency of alpha-fucosylation than a benzoyl group at O-4. It is hypothesized that this is a result of the ability of a benzoyl group at O-3 to participate in glycosyl cation stabilization.

Pig-to-human xenotransplantation might be an option to overcome the increasing shortage of human donor organs. However, naturally occurring antibodies in human blood against the Galalpha1-->3Gal antigen on pig endothelial cells lead to hyperacute or, if prevented, acute or delayed vascular rejection of the pig graft. The purpose of this study was therefore to evaluate synthetic oligosaccharides with terminal Galalpha1-->3Gal to inhibit antigen-binding and cytotoxicity of anti-alphaGal antibodies against pig cells. Different oligosaccharides were synthesized chemically and by a combined chemico-enzymatic approach. These included monomeric di-, tri-, and pentasaccharides, a polyacrylamide-conjugate (PAA-Bdi), as well as di-, tetra-, and octamers of Galalpha1-->3Gal. All were tested for inhibitory activity by anti-alphaGal ELISA and complement-dependent cytotoxicity tests. PAA-Bdi was the best inhibitor of binding as well as cytotoxicity of anti-alphaGal antibodies. Monomeric oligosaccharides efficiently prevented binding of anti-alphaGal IgG, but less well that of anti-alphaGal IgM, with tri- and pentasaccharides showing a better efficacy than the disaccharide. The two trisaccharides Galalpha1-->3Galbeta1-->4GlcNAc and Galalpha1-->3Galbeta1-->3GlcNAc were equally effective. Oligomers of Galalpha1-->3Gal were more effective than monomers in blocking the binding of anti-alphaGal IgG. However, they could not block IgM binding, nor could they match the efficacy of PAA-Bdi. We conclude that oligosaccharides with terminal Galalpha1-->3Gal, most effectively as PAA-conjugates, can prevent binding and cytotoxicity of human anti-alphaGal in vitro. The PAA-Bdi conjugate might be most suited for use as a Sepharose-bound immunoabsorption material.

A series of polydentate dendritic neoglycoconjugates which contain 4, 8, 16, and 32 B-disaccharide ligands were designed as probes to assess the influence of inter-ligand distances on binding to anti-B-disaccharide immunoglobulins.

The effect of the nature of the substituent at O-4 on the stereoselectivity of glycosylation by 2,3-di-O-benzylfucosyl bromides was studied by direct chemical experiments and computer modelling.