Cyclooxygenase-2 isozyme is a promising anti-inflammatory drug target, and overexpression of this enzyme is also associated with several cancers and neurodegenerative diseases. The amino-acid sequence and structural similarity between inducible cyclooxygenase-2 and housekeeping cyclooxygenase-1 isoforms present a significant challenge to design selective cyclooxygenase-2 inhibitors. Herein, we describe the use of the cyclooxygenase-2 active site as a reaction vessel for the in situ generation of its own highly specific inhibitors. Multi-component competitive-binding studies confirmed that the cyclooxygenase-2 isozyme can judiciously select most appropriate chemical building blocks from a pool of chemicals to build its own highly potent inhibitor. Herein, with the use of kinetic target-guided synthesis, also termed as in situ click chemistry, we describe the discovery of two highly potent and selective cyclooxygenase-2 isozyme inhibitors. The in vivo anti-inflammatory activity of these two novel small molecules is significantly higher than that of widely used selective cyclooxygenase-2 inhibitors. Traditional inflammation and pain relief drugs target both cyclooxygenase 1 and 2 (COX-1 and COX-2), causing severe side effects. Here, the authors use in situ click chemistry to develop COX-2 specific inhibitors with high in vivo anti-inflammatory activity.

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In situ click chemistry generation of cyclooxygenase-2 inhibitors

Single cell transcriptomics (scRNA-seq) has transformed our ability to discover and annotate cell types and states, but deep biological understanding requires more than a taxonomic listing of clusters. As new methods arise to measure distinct cellular modalities, including high-dimensional immunophenotypes, chromatin accessibility, and spatial positioning, a key analytical challenge is to integrate these datasets into a harmonized atlas that can be used to better understand cellular identity and function. Here, we develop a computational strategy to "anchor" diverse datasets together, enabling us to integrate and compare single cell measurements not only across scRNA-seq technologies, but different modalities as well. After demonstrating substantial improvement over existing methods for data integration, we anchor scRNA-seq experiments with scATAC-seq datasets to explore chromatin differences in closely related interneuron subsets, and project single cell protein measurements onto a human bone marrow atlas to annotate and characterize lymphocyte populations. Lastly, we demonstrate how anchoring can harmonize in-situ gene expression and scRNA-seq datasets, allowing for the transcriptome-wide imputation of spatial gene expression patterns, and the identification of spatial relationships between mapped cell types in the visual cortex. Our work presents a strategy for comprehensive integration of single cell data, including the assembly of harmonized references, and the transfer of information across datasets. Availability: Installation instructions, documentation, and tutorials are available at: https://www.satijalab.org/seurat

https://biorxiv.org/content/biorxiv/early/2018/11/02/460147.full-text.pdf

Comprehensive integration of single cell data

Isogenic strain construction and gene mapping in Candida albicans.

Microwave assisted synthesis – a critical technology overview

1 Review 1.1 Overview 1.2 Solid-phase organic synthesis (SPOS) 1.3 Beyond conventional solid-phase organic synthesis 1.4 The review 1.5 Some definitions 1.6 Solid-supported reagents and scavengers 1.7 Multi-step use of solid-supported reagents and scavenging reagents 1.8 Conclusions and future perspective 2 Introduction to the tables 2.1 Organisation of tables (reagent and catalyst section) 2.2 Representative data entry (reagent and catalyst section) 2.3 Organisation of tables (scavenging agents section) 2.4 Representative data entry (scavenging agents section) 3 Tables of reagents and catalysts 4 Tables of scavengers 5 Other relevant reviews 5.1 Insoluble polymers 5.1.1 Structure and physical properties (insoluble polymers) 5.1.2 General (insoluble polymers) 5.1.3 Reactions (insoluble polymers) 5.1.4 Miscellaneous (insoluble polymers) 5.2 Soluble polymers 5.2.1 General (soluble polymers) 5.2.2 Reactions (soluble polymers) 5.3 Inorganic solids 5.3.1 Structure and physical properties (inorganic solids) 5.3.2 General (inorganic solids) 5.3.3 Reactions (inorganic solids) 5.3.4 Miscellaneous (inorganic solids) 5.4 Miscellaneous supports 5.4.1 Structure and physical properties (miscellaneous supports) 5.4.2 General (miscellaneous supports) 5.4.3 Reactions (miscellaneous supports) 5.4.4 Miscellaneous (miscellaneous supports) 5.5 Purification strategies 5.5.1 Various supports (purification strategies) 5.5.2 Insoluble polymers (purification strategies) 6 Acknowledgements 7 Abbreviations 8 References 1 Review

Multi-step organic synthesis using solid-supported reagents and scavengers: a new paradigm in chemical library generation

Production of multiple xylanolytic and cellulolytic enzymes by thermophilic fungus Myceliophthora sp. IMI 387099.

Purification and characterization of two endoglucanases from Melanocarpus sp. MTCC 3922.

Alkylating agents have been used for the treatment of cancer for over six decades, yet their repertoire continues to grow. These agents act during all phases of the cell cycle, directly on DNA, cro...

Alkylating agents and cancer therapy

https://scielo.conicyt.cl/pdf/ejb/v10n2/a10.pdf

Jatinder Kaur

Papers

In situ click chemistry generation of cyclooxygenase-2 inhibitors

Production of multiple xylanolytic and cellulolytic enzymes by thermophilic fungus Myceliophthora sp. IMI 387099.

Purification and characterization of two endoglucanases from Melanocarpus sp. MTCC 3922.

Alkylating agents and cancer therapy

Purification and characterization of ß-glucosidase from Melanocarpus sp. MTCC 3922