Modular, Step-Efficient Palladium-Catalyzed Cross-Coupling Strategy To Access C6-Heteroaryl 2-Aminopurine Ribonucleosides.

Two Pd-catalyzed methods to access 6-heteroaryl 2-aminopurine ribonucleosides from 6-chloroguanosine are described. First, Pd-132-catalyzed Suzuki-Miyaura cross-coupling using a series of boron substrates and 6-chloroguanosine forms 6-heteroaryl-2-aminopurines in a single step. The versatility of 6-chloroguanosine is further demonstrated using a modified Sonogashira coupling employing potassium iodide as an additive.

Palladium-Mediated Synthesis of a Near-Infrared Fluorescent K Sensor.

Potassium (K) exits electrically excitable cells during normal and pathophysiological activity. Currently, K-sensitive electrodes and electrical measurements are the primary tools to detect K fluxes. Here, we describe the synthesis of a near-IR, oxazine fluorescent K sensor (K-1) with a dissociation constant suited for detecting changes in intracellular and extracellular K concentrations.

Synthetic biological approaches for RNA labelling and imaging: design principles and future opportunities.

RNA is the most mercurial of all biomacromolecules. In contrast to DNA, where the predominant role is the storage of genetic information, the biological role of RNA varies; ranging from a template-based intermediary in gene expression to playing a direct role in catalysis. Their high turnover and metabolic lability makes the detection of specific sequences particularly challenging.

Pyrrole-Imidazole Polyamides: Manual Solid-Phase Synthesis.

Pyrrole-imidazole polyamides (PAs) are a family of DNA-binding peptides that bind in the minor groove of double-stranded DNA (dsDNA) in a sequence-selective, programmable fashion. This protocol describes a detailed manual procedure for the solid-phase synthesis of this family of compounds. The protocol entails solution-phase synthesis of the Boc-protected pyrrole (Py) and imidazole (Im) carboxylic acid building blocks.

A trifluoroacetic acid-labile sulfonate protecting group and its use in the synthesis of a near-IR fluorophore.

Sulfonated molecules exhibit high water solubility, a property that is valuable for many biological applications but often complicates their synthesis and purification. Here we report a sulfonate protecting group that is resistant to nucleophilic attack but readily removed with trifluoroacetic acid (TFA). The use of this protecting group improved the synthesis of a sulfonated near-IR fluorophore and the mild deprotection conditions allowed isolation of the product without requiring chromatography.

Synthesis of near-IR fluorescent oxazine dyes with esterase-labile sulfonate esters.

Near-IR oxazine dyes are reported that contain sulfonate esters which are rapidly cleaved by esterase activity to unmask highly polar anionic sulfonates. Strategies for the synthesis of these dyes included the development of milder dye condensation conditions with improved functional compatibility and the use of an alkyl halide that allows for the introduction of esterase-labile sulfonates without the need for sulfonation of the target molecule.