There is now a great deal of interest in group 13, 14, and 15 elements in low coordination states.1 Since 1981, several new compounds of the type M=M/ (M and M': group 13, 14, and 15 elements) withbonds have been reported. In organogermanium chemistry, the first stable derivatives with a sp2-hybridized germanium have only been prepared very recently: they are the digermenes R2Ge=GeR22 (R = bis(trimethylsilvl) methyl,23 2,6-dimethylphenyl,2b 2,6-diethylphenyl2c), the germaphosphene
The structural novelty of lead compounds is very important in the agrochemical and pharmaceutical industries, and as such, natural products can be an important source. Taking into account that the isolation of lead compounds is very time-consuming, the efficient and safe identification of compounds in microorganism and plant extracts isolated previously is essential. A suitable procedure for this task based on an HPLC system interfaced with an electrospray (ESI) source and a Thermo Finnigan LCQ deca XP plus ion-trap mass spectrometer was developed, and an extensive MS/MS spectral library of characterized natural products was built up. This report summarizes the parameters used for acquiring the library spectra and discusses current limitations of the NIST library and search algorithm. The advantages of the newly introduced Mass Frontier 4.0 for the search of MS/MS product-ion spectra are discussed. Different mechanisms for fragmentation of some [M + H](+) and [M + Na](+) ions that were found are proposed. Oligomycin A, a macrolide antibiotic, exhibits different fragmentation mechanisms in positive and negative ion modes. The cleavage of the ester bond is the preferred mechanism in the positive ion mode, whereas two different pathways-one showing a rare retro-Michael-addition-are observed in the negative ion mode.
The solution structures of the lantibiotics duramycin B in H,O/'H,O (9 : 1) and duramycin C in (2H,)acetonitrile/H,0 (1 : 1) have been determined by NMR followed by distance-geometry and restrained-molecular-mechanics calculations. The constitution and location of three thioether bridges and a lysinoalanine ring system could be established by unambiguously assigned NOE contacts between the bridging side chains. Model building based on NMR constraints resulted in a U-shaped topology of the tetracyclic 19-peptides with a turn around Pro9 and a kink along a virtual line from residues 5 to 13. This clamp-like conformation is stabilized by the thioether bridges and is additionally supported by an antiparallel P-strand-like structure of the N-termini and C-termini and the inherent amphiphilicity of duramycin-type lantibiotics. The duramycins B and C differ mainly in the relative mobilities of their rings A, C and D. Duramycin B is closely related to cinnamycin with an exchange of PhelO to leucine, whereas duramycin C differs from duramycin B by three conserved and two non-conserved amino-acid exchanges.The duramycins B and C belong to the class of heterodet polycyclic peptide antibiotics which were named lantibiotics [ l , 21. Their common structural elements are thioether rings formed by lanthionine and 3-methyl-lanthionine residues. Further unusual amino acid residues occur in the duramycin family such as 3-hydroxy-aspartic acid and a lysinoalanine bridge. The duramycins B and C have been isolated as inhibitors of phospholipase A, with activities in the micromolar range [3]. They show specific interaction with phosphatidylethanolamine, but not with the closely related phosphatidylcholine [4].Lantibiotics share a common biosynthesis pathway which involves the ribosomal synthesis of a prepeptide with a Nterminal leader sequence followed by post-translational modification and processing [5]. The modification involves enzymic dehydration of the serine and threonine residues in the C-terminal propeptide part to didehydroalanine and 2,3-didehydrobutyrine. Through stereospecific addition of the thiol group of cysteine residues to the double bonds of the Abbreviations. NOESY, nuclear Overhauser enhancement spectroscopy ; COSY, correlated spectroscopy ; DQF, double quantum filter; TOCSY, total correlation spectroscopy; HMQC, heteronuclear multiple quantum coherence; HMBC, heteronucledr multiple bond correlation; DISCO, differences and sums of COSY spectra; ROESY, rotating frame nuclear overhauser enhancement spectroscopy ; Ah,, L-alanine moiety of (2S,6R)-lanthionine and (2S,3S,6R)-methyllanthionine; D-Ala,, D-alanine moiety of (2S,6R)-lanthionine; Abu, (2S,3S)-p-methylalanine moiety of (2S,3S,6R)-methyllanthionine; Ala,, L-alanine moiety of (2S,9S)-lysinoalanine; HyAsp, (2S,3R)-3-hydroxy-aspartic acid; MD, molecular dynamics.Dedication. Dedicated to Prof. Murray Goodman on occasion of his 65th birthday.2,3-didehydroamino acid residues, the thioether bridges of lanthionine and b-methyl-lanthionine are formed. Addition of lys...
Duramycins B and C, two new lanthionine containing antibiotics, have been isolated from Streptoverticillium strain R2075 and Streptomyces griseoluteus (R2107). The known antibiotics duramycin and cinnamycin were reisolated from Streptoverticillium hachijoense (DSM401 14) and Streptomyces longisporoflavus (DSM40165). The structures of these latter two compoundsshould be revised by changing amino acid residue 3 to glutamine and 17 to asparagine, respectively.Cinnamycin therefore seems to be identical to Ro 09-0198. Leucopeptin has been shown to be identical to duramycin. Physico-chemical data of these compounds provide evidence for a similar structure for all duramycin antibiotics. All compoundsof this group inhibit humanphospholipase A2 at a concentration of 10~6 molar.Phospholipase A2 [EC 3.1.1.4] plays a major role in the release ofarachidonic acid from phospholipids in the cell membranes1*. Further oxidative metabolism of free arachidonic acid leads to prostaglandins and leukotrienes2).Several of these eicosanoids are potent mediators of diseases, such as inflammation and allergy3). Inhibition of the enzymic activity of phospholipase A2 may therefore be therapeutically beneficial.In our search for naturally occurring inhibitors of phospholipase A2 among secondary metabolites of microorganisms two newinhibitors from the actinomycetes strains R2075 and R2107 were identified which appeared to be closely related to the known peptide antibiotic duramycin. Using a different screening assay for compounds stimulating DNArepair, we found a strain producing duramycin as well as one producing cinnamycin (W. Marki and E. Rommele; unpublished results). In the present communication the taxonomy of these strains and the production, isolation, physico-chemical data and phospholipase inhibition of the newcompoundsduramycins B and C, as well as of duramycin and cinnamycin are described. Experimental results relating to the structural characterization are presented as well. Materials and Methods Microorganism
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