The Production and Fate of Volatile Organosulfur Compounds in Sulfidic and Ferruginous Sediment

Volatile organic sulfur compounds (VOSCs) link the atmospheric, marine, and terrestrial sulfur cycles in marine and marginal marine environments. Despite the important role VOSCs play in global biogeochemical sulfur cycling, less is known about how the local geochemical conditions influence production and consumption of VOSCs. We present a study of dimethyl sulfide (DMS), methanethiol (MeSH), and dimethylsulfoniopropionate (DMSP) in sulfide-rich (sulfidic) and iron-rich (ferruginous) salt marsh sediment from north Norfolk, UK. Initial results illustrate the importance of minimizing time between sampling in remote field locations and laboratory analysis, due to rapid degradation of VOSCs. With rapid analysis of sediment from different depths, we observe high concentrations of DMS, MeSH, and DMSP, with concentrations in surface sediment an order of magnitude higher than those in previous studies of surface water. We measure systematic differences in the concentration and depth distribution of MeSH and DMS between sediment environments; DMS concentrations are higher in ferruginous sediment, and MeSH concentrations are higher in sulfidic sediment. With repeated measurements over a short time period, we show that the degradation patterns for DMS and MeSH are different in the ferruginous versus sulfidic sediment. We discuss potential biogeochemical interactions that could be driving the observed differences in VOSC dynamics in ferruginous and sulfidic sediment.This work was supported by a Churchill Scholarship to J. V. W., NERC Grant NE/S001352/1 to A.V.T. and J. D. T., NERC Grant NE/K01546X/1 to K. R. R., and NERC Grants NE/P012671/1, NE/N002385/1, and NE/M004449/1 to J. D. T. Initial analyses were supported by ERCStG307582 (CARBONSINK) to A. V. T

Macrocyclisation of small peptides enabled by oxetane incorporation

Cyclic peptides are an important source of new drugs but are challenging to produce synthetically. We show that head-to-tail peptide macrocyclisations are greatly improved, as measured by isolated yields, reaction rates and product distribution, by substitution of one of the backbone amide C═O bonds with an oxetane ring. The cyclisation precursors are easily made by standard solution- or solid-phase peptide synthesis techniques. Macrocyclisations across a range of challenging ring sizes (tetra-, penta- and hexapeptides) are enabled by incorporation of this turn-inducing element. Oxetane incorporation is shown to be superior to other established amino acid modifications such as N-methylation. The positional dependence of the modification on cyclisation efficiency is mapped using a cyclic peptide of sequence LAGAY. We provide the first direct experimental evidence that oxetane modification induces a turn in linear peptide backbones, through the observation of dNN (i, i + 2) and dαN (i, i + 2) NOEs, which offers an explanation for these improvements. For cyclic peptide, cLAGAY, a combination of NMR derived distance restraints and molecular dynamics simulations are used to show that this modification alters the backbone conformation in proximity to the oxetane, with the flexibility of the ring reduced and a new intramolecular H-bond established. Finally, we incorporated an oxetane into a cyclic pentapeptide inhibitor of Aminopeptidase N, a transmembrane metalloprotease overexpressed on the surface of cancer cells. The inhibitor, cCNGRC, displayed similar IC50 values in the presence or absence of an oxetane at the glycine residue, indicating that bioactivity is fully retained upon amide C═O bond replacement

Utility of the pooling approach as applied to whole genome association scans with high-density Affymetrix microarrays

Background: We report an attempt to extend the previously successful approach of combining SNP (single nucleotide polymorphism) microarrays and DNA pooling (SNP-MaP) employing high-density microarrays. Whereas earlier studies employed a range of Affymetrix SNP microarrays comprising from 10 K to 500 K SNPs, this most recent investigation used the 6.0 chip which displays 906,600 SNP probes and 946,000 probes for the interrogation of CNVs (copy number variations). The genotyping assay using the Affymetrix SNP 6.0 array is highly demanding on sample quality due to the small feature size, low redundancy, and lack of mismatch probes. Findings: In the first study published so far using this microarray on pooled DNA, we found that pooled cheek swab DNA could not accurately predict real allele frequencies of the samples that comprised the pools. In contrast, the allele frequency estimates using blood DNA pools were reasonable, although inferior compared to those obtained with previously employed Affymetrix microarrays. However, it might be possible to improve performance by developing improved analysis methods. Conclusions: Despite the decreasing costs of genome-wide individual genotyping, the pooling approach may have applications in very large-scale case-control association studies. In such cases, our study suggests that high-quality DNA preparations and lower density platforms should be preferred

The Production and Fate of Volatile Organosulfur Compounds in Sulfidic and Ferruginous Sediment

Volatile organic sulfur compounds (VOSCs) link the atmospheric, marine, and terrestrial sulfur cycles in marine and marginal marine environments. Despite the important role VOSCs play in global biogeochemical sulfur cycling, less is known about how the local geochemical conditions influence production and consumption of VOSCs. We present a study of dimethyl sulfide (DMS), methanethiol (MeSH), and dimethylsulfoniopropionate (DMSP) in sulfide-rich (sulfidic) and iron-rich (ferruginous) salt marsh sediment from north Norfolk, UK. Initial results illustrate the importance of minimizing time between sampling in remote field locations and laboratory analysis, due to rapid degradation of VOSCs. With rapid analysis of sediment from different depths, we observe high concentrations of DMS, MeSH, and DMSP, with concentrations in surface sediment an order of magnitude higher than those in previous studies of surface water. We measure systematic differences in the concentration and depth distribution of MeSH and DMS between sediment environments; DMS concentrations are higher in ferruginous sediment, and MeSH concentrations are higher in sulfidic sediment. With repeated measurements over a short time period, we show that the degradation patterns for DMS and MeSH are different in the ferruginous versus sulfidic sediment. We discuss potential biogeochemical interactions that could be driving the observed differences in VOSC dynamics in ferruginous and sulfidic sediment.This work was supported by a Churchill Scholarship to J. V. W., NERC Grant NE/S001352/1 to A.V.T. and J. D. T., NERC Grant NE/K01546X/1 to K. R. R., and NERC Grants NE/P012671/1, NE/N002385/1, and NE/M004449/1 to J. D. T. Initial analyses were supported by ERCStG307582 (CARBONSINK) to A. V. T