PGFinder, a novel analysis pipeline for the consistent, reproducible, and high-resolution structural analysis of bacterial peptidoglycans

Many software solutions are available for proteomics and glycomics studies, but none are ideal for the structural analysis of peptidoglycan (PG), the essential and major component of bacterial cell envelopes. It icomprises glycan chains and peptide stems, both containing unusual amino acids and sugars. This has forced the field to rely on manual analysis approaches, which are time-consuming, labour-intensive, and prone to error. The lack of automated tools has hampered the ability to perform high-throughput analyses and prevented the adoption of a standard methodology. Here, we describe a novel tool called PGFinder for the analysis of PG structure and demonstrate that it represents a powerful tool to quantify PG fragments and discover novel structural features. Our analysis workflow, which relies on open-access tools, is a breakthrough towards a consistent and reproducible analysis of bacterial PGs. It represents a significant advance towards peptidoglycomics as a full-fledged discipline.

Natural Products Containing ‘Rare’ Organophosphorus Functional Groups

Phosphorous-containing molecules are essential constituents of all living cells. While the phosphate functional group is very common in small molecule natural products, nucleic acids, and as chemical modification in protein and peptides, phosphorous can form P–N (phosphoramidate), P–S (phosphorothioate), and P–C (e.g., phosphonate and phosphinate) linkages. While rare, these moieties play critical roles in many processes and in all forms of life. In this review we thoroughly categorize P–N, P–S, and P–C natural organophosphorus compounds. Information on biological source, biological activity, and biosynthesis is included, if known. This review also summarizes the role of phosphorylation on unusual amino acids in proteins (N- and S-phosphorylation) and reviews the natural phosphorothioate (P–S) and phosphoramidate (P–N) modifications of DNA and nucleotides with an emphasis on their role in the metabolism of the cell. We challenge the commonly held notion that nonphosphate organophosphorus functional groups are an oddity of biochemistry, with no central role in the metabolism of the cell. We postulate that the extent of utilization of some phosphorus groups by life, especially those containing P–N bonds, is likely severely underestimated and has been largely overlooked, mainly due to the technological limitations in their detection and analysis.

Syntheses of Cyclomarins – Interesting Marine Natural Products with Distinct Mode of Action towards Malaria and Tuberculosis

The cyclomarins are cyclic heptapeptides from marine streptomycetes containing four rather unusual amino acids. Interestingly, the cyclomarins address two completely different targets: ClpC1, a subunit of the caseinolytic protease of Mycobacterium tuberculosis (MTB), as well as PfAp3Aase of Plasmodium falciparum. Therefore, the cyclomarins are interesting lead structures for the development of drugs targeting tuberculosis and malaria. As a result, several synthetic protocols towards the synthesis of these unusual building blocks as well as the natural products themselves have been developed, which will be discussed in this review.1 Introduction2 Synthesis of the Building Blocks3 Total Synthesis of Cyclomarin C by Yao and Co-workers4 Total Synthesis of Cyclomarin A and C by Barbie and Kazmaier5 Conclusion

Design and Synthesis of Aromatics through [2+2+2] Cyclotrimerization

The [2+2+2] cycloaddition reaction is a useful tool to realize unusual chemical transformations which are not achievable by traditional methods. Here, we report our work during the past two decades that involve utilization of transition-metal complexes in a [2+2+2] cyclotrimerization reaction. Several key “building blocks” were assembled by a [2+2+2] cycloaddition approach and they have been further expanded by other synthetic transformations to design unusual amino acids and peptides, diphenylalkanes, bis- and trisaryl benzene derivatives, annulated benzocycloalkanes, spirocycles, and spirooxindole derivatives. Furthermore, we have also discussed about alkyne surrogates, environmentally friendly, and stereoselective [2+2+2] cycloaddition reactions. Application of the [2+2+2] cycloaddition reaction in total synthesis is also covered. In this review we also included others work to give a balanced view of the recent developments in the area of [2+2+2] cycloaddition.1 Introduction2 Unusual Amino Acids and Peptides3 Heteroanalogues of Indane4 Diphenylalkane Derivatives5 Multi-Armed Aryl Benzene Derivatives6 Annulated Benzocycloalkanes7 Spirocycles8 Selectivity in [2+2+2] Cycloaddition of Alkynes9 [2+2+2] Cycloaddition Reactions under Environmentally Friendly Conditions10 Alkyne Surrogates11 Domino Reactions involving a [2+2+2] Cycloaddition12 Biologically Important Targets/Total Synthesis13 Conclusions