A Phosphotriester-Masked Dideoxy-cGAMP Derivative as a Cell-Permeable STING Agonist.

2',3'-Cyclic GMP-AMP (cGAMP) is a cyclic dinucleotide second messenger in which guanosine and adenosine are connected by one 3'-5' and one 2'-5' phosphodiester linkage. It is formed in the cytosol upon detection of pathogenic DNA by the enzyme guanosine-monophosphate-adenosine monophosphate synthase (cGAS). cGAMP subsequently binds to the adaptor protein stimulator of interferon genes (STING) to elicit an innate immune response leading to the production of type I interferons and cytokines.

High-throughput bactericidal assays for monoclonal antibody screening against antimicrobial resistant .

(gonococcus) is an obligate human pathogen and the etiological agent of the sexually transmitted disease gonorrhea. The rapid rise in gonococcal resistance to all currently available antimicrobials has become a significant public health burden and the need to develop novel therapeutic and prophylactic tools is now a global priority. While high-throughput screening methods allowed rapid discovery of extremely potent monoclonal antibodies (mAbs) against viral pathogens, the field of bacteriology suffers from the lack of assays that allow efficient screening of large panels of samples.

A new dawn for monoclonal antibodies against antimicrobial resistant bacteria.

Antimicrobial resistance (AMR) is a quickly advancing threat for human health worldwide and almost 5 million deaths are already attributable to this phenomenon every year. Since antibiotics are failing to treat AMR-bacteria, new tools are needed, and human monoclonal antibodies (mAbs) can fill this role. In almost 50 years since the introduction of the first technology that led to mAb discovery, enormous leaps forward have been made to identify and develop extremely potent human mAbs.

Novel Poxin Stable cGAMP-Derivatives Are Remarkable STING Agonists.

2',3'-cGAMP is a cyclic A- and G-containing dinucleotide second messenger, which is formed upon cellular recognition of foreign cytosolic DNA as part of the innate immune response. The molecule binds to the adaptor protein STING, which induces an immune response characterized by the production of type I interferons and cytokines. The development of STING-binding molecules with both agonistic as well as antagonistic properties is currently of tremendous interest to induce or enhance antitumor or antiviral immunity on the one hand, or to treat autoimmune diseases on the other hand.

A Click Chemistry Approach to Developing Molecularly Targeted DNA Scissors.

Nucleic acid click chemistry was used to prepare a family of chemically modified triplex forming oligonucleotides (TFOs) for application as a new gene-targeted technology. Azide-bearing phenanthrene ligands-designed to promote triplex stability and copper binding-were 'clicked' to alkyne-modified parallel TFOs. Using this approach, a library of TFO hybrids was prepared and shown to effectively target purine-rich genetic elements in vitro.

Supersensitive Multifluorophore RNA-FISH for Early Virus Detection and Flow-FISH by Using Click Chemistry.

The reliable detection of transcription events through the quantification of the corresponding mRNA is of paramount importance for the diagnostics of infections and diseases. The quantification and localization analysis of the transcripts of a particular gene allows disease states to be characterized more directly compared to an analysis on the transcriptome wide level. This is particularly needed for the early detection of virus infections as now required for emergent viral diseases, e.

A Click-Chemistry Linked 2'3'-cGAMP Analogue.

2'3'-cGAMP is an uncanonical cyclic dinucleotide where one A and one G base are connected via a 3'-5' and a unique 2'-5' linkage. The molecule is produced by the cyclase cGAS in response to cytosolic DNA binding. cGAMP activates STING and hence one of the most powerful pathways of innate immunity.

Dendrimer-Based Signal Amplification of Click-Labelled DNA in Situ.

The in vivo incorporation of alkyne-modified bases into the genome of cells is today the basis for the efficient detection of cell proliferation. Cells are grown in the presence of ethinyl-dU (EdU), fixed and permeabilised. The incorporated alkynes are then efficiently detected by using azide-containing fluorophores and the Cu -catalysed alkyne-azide click reaction.

5-Formylcytosine Could Be a Semipermanent Base in Specific Genome Sites.

5-Formyl-2'-deoxycytosine (fdC) is a recently discovered epigenetic base in the genome of stem cells, with yet unknown functions. Sequencing data show that the base is enriched in CpG islands of promoters and hence likely involved in the regulation of transcription during cellular differentiation. fdC is known to be recognized and excised by the enzyme thymine-DNA-glycosylase (Tdg).