Solid-Phase Synthesis of Caged Luminescent Peptides via Side Chain Anchoring.

The synthesis of caged luminescent peptide substrates remains challenging, especially when libraries of the substrates are required. Most currently available synthetic methods rely on a solution-phase approach, which is less suited for parallel synthesis purposes. We herein present a solid-phase peptide synthesis (SPPS) method for the synthesis of caged aminoluciferin peptides via side chain anchoring of the P residue.

Synthesis and Evaluation of Glycosyl Luciferins.

Measuring glycosidase activity is important to monitor any aberrations in carbohydrate hydrolase activity, but also for the screening of potential glycosidase inhibitors. To this end, synthetic substrates are needed which provide an enzyme-dependent read-out upon hydrolysis by the glycosidase. Herein, we present two new routes for the synthesis of caged luminescent carbohydrates, which can be used for determining glycosidase activity with a luminescent reporter molecule.

Activity Sensing of Coagulation and Fibrinolytic Proteases.

The blood coagulation cascade is a complex physiological process involving the action of multiple coupled enzymes, cofactors, and substrates, ultimately leading to clot formation. Serine proteases have a crucial role, and aberrations in their activity can lead to life-threatening bleeding disorders and thrombosis. This review summarizes the essential proteases involved in blood coagulation and fibrinolysis, the endogenous peptide sequences they recognize and hydrolyze, and synthetic peptide probes based on these sequences to measure their activity.

Readily Accessible Strained Difunctionalized trans-Cyclooctenes with Fast Click and Release Capabilities.

The click reaction between a functionalized trans-cyclooctene (TCO) and a tetrazine (Tz) is a compelling method for bioorthogonal conjugation in combination with payload releasing capabilities. However, the synthesis of difunctionalized TCOs remains challenging. As a result, these compounds are poorly accessible, which impedes the development of novel applications.

Investigation of in vitro histone H3 glycosylation using H3 tail peptides.

Posttranslational modifications (PTMs) on histone tails regulate eukaryotic gene expression by impacting the chromatin structure and by modulating interactions with other cellular proteins. One such PTM has been identified as serine and threonine glycosylation, the introduction of the ß-N-acetylglucosamine (GlcNAc) moiety on histone H3 tail at position Ser10 and Thr32. The addition of the ß-O-GlcNAc moiety on serine or threonine residues is facilitated by the O-GlcNAc transferase (OGT), and can be removed by the action of O-GlcNAcase (OGA).

Luminescent Assay for the Screening of SARS-CoV-2 M Inhibitors.

Since the outbreak of SARS-CoV-2 in December 2019 millions of infections have been reported globally. The viral chymotrypsin-like main protease (M ) exhibits a crucial role in viral replication and represents a relevant target for antiviral drug development. In order to screen potential M inhibitors we developed a luminescent assay using a peptide based probe containing a cleavage site specific for M .

A Revised Modular Approach to (-)--Δ-THC and Derivatives Through Late-Stage Suzuki-Miyaura Cross-Coupling Reactions.

A revised modular approach to various synthetic (-)--Δ-THC derivatives through late-stage Suzuki-Miyaura cross-coupling reactions is disclosed. Ten derivatives were synthesized allowing both sp- and sp-hybridized cross-coupling partners with minimal β-hydride elimination. Importantly, we demonstrate that a -bromo-substituted THC scaffold for Suzuki-Miyaura cross-coupling reactions has been initially reported incorrectly in recent literature.