New Halogenated Secondary Metabolites from Red Algae of the South Pacific

<p>An NMR- and MS-directed study led to the isolation and structure elucidation of several halogenated secondary metabolites from a New Zealand and a Tongan red alga. An extensive investigation was carried out on the New Zealand red alga Rhodophyllis membranacea following mass spectrometric evidence for an unusual tetrahalogenated indole with the exceptionally rare inclusion of bromine, chlorine and iodine within a fraction of a semi-purified extract. Due to the difficulty associated with the structure elucidation of proton deficient molecules, a strategic isolation and structure elucidation of several polyhalogenated indoles was employed in order to unequivocally assign the halogen positions on the indolic core. This resulted in the isolation and characterisation of 11 new tetrahalogenated indoles (123–133), four of which contain bromine, chlorine and iodine (124 and 129–131) and represent the first isolation of such compounds. Additionally, four new pentahalogenated indoles (134–137) and an uncharacterised tribromotrichloroindole were isolated. The synthetically known compound 4-chloroisatin (138) was isolated as a new marine natural product, while 4-chloro-3-hydroxyl-3-(2-oxopropyl)-2-oxindole (139) was established to be an artefact of isolation. Several compounds were found to exhibit antifungal properties against Saccharomyces cerevisiae. A detailed examination of the Tongan alga Callophycus serratus led to the isolation of six new meroditerpenoids: callophycol C (227), iodocallophycols E (228) and F (229), iodocallophycoic acid B (230), deiodocallophycoic B (231) and callophycoic acid I (232). The relative configurations in compounds 228–231 are proposed to differ from closely related compounds in the literature. Iodocallophycol E (228) exhibited moderate cytotoxicity against the HL-60 cell line with an IC50 value of 6.0 μM.</p>

New Halogenated Secondary Metabolites from Red Algae of the South Pacific

<p>An NMR- and MS-directed study led to the isolation and structure elucidation of several halogenated secondary metabolites from a New Zealand and a Tongan red alga. An extensive investigation was carried out on the New Zealand red alga Rhodophyllis membranacea following mass spectrometric evidence for an unusual tetrahalogenated indole with the exceptionally rare inclusion of bromine, chlorine and iodine within a fraction of a semi-purified extract. Due to the difficulty associated with the structure elucidation of proton deficient molecules, a strategic isolation and structure elucidation of several polyhalogenated indoles was employed in order to unequivocally assign the halogen positions on the indolic core. This resulted in the isolation and characterisation of 11 new tetrahalogenated indoles (123–133), four of which contain bromine, chlorine and iodine (124 and 129–131) and represent the first isolation of such compounds. Additionally, four new pentahalogenated indoles (134–137) and an uncharacterised tribromotrichloroindole were isolated. The synthetically known compound 4-chloroisatin (138) was isolated as a new marine natural product, while 4-chloro-3-hydroxyl-3-(2-oxopropyl)-2-oxindole (139) was established to be an artefact of isolation. Several compounds were found to exhibit antifungal properties against Saccharomyces cerevisiae. A detailed examination of the Tongan alga Callophycus serratus led to the isolation of six new meroditerpenoids: callophycol C (227), iodocallophycols E (228) and F (229), iodocallophycoic acid B (230), deiodocallophycoic B (231) and callophycoic acid I (232). The relative configurations in compounds 228–231 are proposed to differ from closely related compounds in the literature. Iodocallophycol E (228) exhibited moderate cytotoxicity against the HL-60 cell line with an IC50 value of 6.0 μM.</p>

Bacterial translation machinery for deliberate mistranslation of the genetic code

Inaccurate expression of the genetic code, also known as mistranslation, is an emerging paradigm in microbial studies. Growing evidence suggests that many microbial pathogens can deliberately mistranslate their genetic code to help invade a host or evade host immune responses. However, discovering different capacities for deliberate mistranslation remains a challenge because each group of pathogens typically employs a unique mistranslation mechanism. In this study, we address this problem by studying duplicated genes of aminoacyl-transfer RNA (tRNA) synthetases. Using bacterial prolyl-tRNA synthetase (ProRS) genes as an example, we identify an anomalous ProRS isoform, ProRSx, and a corresponding tRNA, tRNAProA, that are predominately found in plant pathogens from Streptomyces species. We then show that tRNAProA has an unusual hybrid structure that allows this tRNA to mistranslate alanine codons as proline. Finally, we provide biochemical, genetic, and mass spectrometric evidence that cells which express ProRSx and tRNAProA can translate GCU alanine codons as both alanine and proline. This dual use of alanine codons creates a hidden proteome diversity due to stochastic Ala→Pro mutations in protein sequences. Thus, we show that important plant pathogens are equipped with a tool to alter the identity of their sense codons. This finding reveals the initial example of a natural tRNA synthetase/tRNA pair for dedicated mistranslation of sense codons.

Synthesis of Different Analogs of Ab(9-16) Peptide Mass spectrometric evidence for heavy metal binding

Amyloid-b (Ab) peptides are proteins associated with Alzheimer�s disease (AD), because the extracellular Ab deposits are the main cause of this disorder. The aggregation of Ab has been shown to depend on the interactions with metal ions, such as copper, zinc, aluminum or iron. The N-terminal sequence of Ab(1-42) or Ab(1-40) peptides, namely Ab(1-16) peptide fragment, is considered the metal binding site involved in AD neurodegeneration and amyloidogenesis. Therefore, we have investigated different peptide sequences to understand the role played by some amino acid residues in metal binding. In this paper, we report the chemical synthesis of Ab(9-16) peptide and its analogs by Fmoc/tBu strategy and the mass spectrometric evidence for metal ion binding to newly synthesized peptides. MALDI-ToF mass spectrometry proved to be a reliable tool to detect and identify the metal ion complexes of all peptides investigated with copper, iron and zinc ions.

The contribution of chemical vapor generation coupled with atomic or mass spectrometry to the comprehension of the chemistry of aqueous boranes

Mechanisms of hydride generation by aqueous boranes have been updated in the light of recent atomic and mass spectrometric evidence.