Volume 12 Issue 6, June 2020

Three versatile and mutually orthogonal tRNA/aminoacyl-tRNA synthetase pairs have been developed. Collectively, these pairs enable the site-specific incorporation of three different non-canonical amino acids into a protein that can still be terminated faithfully by a natural stop codon.

The direct conversion of lead compounds into potentially more potent derivatives, through selective functionalization, could help to speed up the discovery of drug candidates. Now, a method has been reported that enables the late-stage C–H methylation of complex drug-like molecules, using a sustainable cobalt-based catalyst.

Identifying chromatin modifications and their interactomes is imperative to understand how chromatin functions and is regulated. Now, two new studies report on chemical tools that enable characterization of the biological interactions within native chromatin.

The use of automation for chemical research and reaction discovery has seen significant advances in recent years, but there are still problems that need to be solved. Ella M. Gale and Derek J. Durand discuss limitations in the field and how researchers are working to address these issues.

Despite the importance of C–H methylation in medicinal chemistry, the application to densely functionalized complex molecules remains a challenge. Now, a novel cobalt-catalysed method takes advantage of inherently present functional groups to guide the C–H activation and a boron-based methyl source enables the late stage C–H methylation of pharmaceutically relevant substrates.

Proteins that interact with histone post-translational modifications have now been identified using an approach based on split-intein mediated histone semisynthesis. Histone modifications and disease-relevant mutations were installed into native chromatin with an adjacent photocross-linker to enable in situ cross-linking. This strategy enabled the determination of chromatin-relevant interactomes and represents a powerful tool for exploring epigenetic regulation and dysregulation at the molecular level.

Scattering experiments in which two beams nearly co-propagate allow broadly tunable collision energies and can enable cold collisions. Now, such experiments have been combined with the preparation of NO molecules using stimulated emission to generate highly vibrationally excited states for state-to-state scattering studies, testing the theoretical gold standard in a regime not found in nature.

Non-canonical amino acids (ncAAs) can be incorporated into proteins in cells using orthogonal aminaocyl–tRNA synthetase/tRNA pairs; the most widely adopted system is based on a pyrrolysyl–tRNA synthetase (PylRS)/tRNA pair. Now, three new PylRS/tRNA pairs have been developed that are mutually orthogonal and can be used together to site-specifically incorporate three distinct ncAAs into a single protein.

The preparation of unprotected alicyclic amines containing variable substituents in multiple ring positions typically requires multistep synthetic sequences. Now, an advance in C–H bond functionalization methodology that enables the convenient preparation of elusive endocyclic 1-azaallyl anions allows the introduction of up to three substituents in a single operation.

The photoinduced dimerization of a prochiral anthracenecarboxylic acid occurs in an enantioselective fashion when the molecules are adsorbed on helical metal nanostructures. This enantiopreference arises mostly from the helicity of the silver and copper substrates—prepared using shear forces during the deposition process—and may also be influenced by chiroplasmonic effects.

Au/C single-site catalysts have been validated commercially for acetylene hydrochlorination, but they have previously been prepared using highly oxidizing acidic solvents or additional ligands. It has now been shown that they can be made by impregnation of a metal salt from an acetone solution—generating catalysts with comparable activity to those synthesized by the other methods.

Inverting the order of nature’s two-phase biosynthesis of terpenes offers a strategy by which the synthesis of these compounds can be simplified. The key reaction is a palladium-catalysed polyenyne cycloisomerization that not only tolerates the presence of all of the oxygen functionalities but also is facilitated by them.

The distortion of an amide group away from a planar conformation typically enhances its reactivity and such activation is usually achieved through the chemical synthesis of twisted amides. Now, it has been shown that a non-covalent activation strategy leading to accelerated hydrolysis can be achieved by binding a reactive twisted amide conformer inside a molecular cage.