Making Sense of “Nonsense” and More: Challenges and Opportunities in the Genetic Code Expansion, in the World of tRNA Modifications

The evolutional development of the RNA translation process that leads to protein synthesis based on naturally occurring amino acids has its continuation via synthetic biology, the so-called rational bioengineering. Genetic code expansion (GCE) explores beyond the natural translational processes to further enhance the structural properties and augment the functionality of a wide range of proteins. Prokaryotic and eukaryotic ribosomal machinery have been proven to accept engineered tRNAs from orthogonal organisms to efficiently incorporate noncanonical amino acids (ncAAs) with rationally designed side chains. These side chains can be reactive or functional groups, which can be extensively utilized in biochemical, biophysical, and cellular studies. Genetic code extension offers the contingency of introducing more than one ncAA into protein through frameshift suppression, multi-site-specific incorporation of ncAAs, thereby increasing the vast number of possible applications. However, different mediating factors reduce the yield and efficiency of ncAA incorporation into synthetic proteins. In this review, we comment on the recent advancements in genetic code expansion to signify the relevance of systems biology in improving ncAA incorporation efficiency. We discuss the emerging impact of tRNA modifications and metabolism in protein design. We also provide examples of the latest successful accomplishments in synthetic protein therapeutics and show how codon expansion has been employed in various scientific and biotechnological applications.

Synthesis of pyrethroids and jasmonoids by palladium-catalyzed cross coupling reactions

The synthesis of jasmone and related jasmonoids and pyrethroids is described. These types of compounds play a defensive role in plants, and share a cyclopentenone common core, with variations in its side chains. Jasmone, cinerone, allylrethrone and derivatives are synthesized through π-allyl palladium cross coupling of stannane derivatives. By selective hydrogenation dihydrojasmone and dihydrocinerone are also synthesized.

Localising individual atoms of tryptophan side chains in the metallo-<i>β</i>-lactamase IMP-1 by pseudocontact shifts from paramagnetic lanthanoid tags at multiple sites

The metallo-β-lactamase IMP-1 features a flexible loop near the active site that assumes different conformations in single crystal structures, which may assist in substrate binding and enzymatic activity. To probe the position of this loop, we labelled the tryptophan residues of IMP-1 with 7-13C-indole and the protein with lanthanoid tags at three different sites. The magnetic susceptibility anisotropy (Δχ) tensors were determined by measuring pseudocontact shifts (PCSs) of backbone amide protons. The Δχ tensors were subsequently used to identify the atomic coordinates of the tryptophan side chains in the protein. The PCSs were sufficient to determine the location of Trp28, which is in the active site loop targeted by our experiments, with high accuracy. Its average atomic coordinates showed barely significant changes in response to the inhibitor captopril. It was found that localisation spaces could be defined with better accuracy by including only the PCSs of a single paramagnetic lanthanoid ion for each tag and tagging site. The effect was attributed to the shallow angle with which PCS isosurfaces tend to intersect if generated by tags and tagging sites that are identical except for the paramagnetic lanthanoid ion.

The effect of side chain engineering on conjugated polymers in organic electrochemical transistors for bioelectronic applications

The versatile synthetic side chain toolbox assists in tuning the OECT parameters by controlling material properties of organic mixed conductors. In this review we critically summarise and evaluate various side chains used throughout OECT materials.

Enhanced Emission by Stacking of Crown Ether Side Chains in A 2D Covalent Organic Framework

Hydrazone compounds could be highly emissive in solid state. However, most hydrazone-linking COFs are poorly luminescent. Here we report the enhancement of fluorescence in a 2D hydrazone-linking COF by side...

Interfacial photocrosslinking of polymer particles possessing nucleobase photoreactive groups for hollow/capsule polymer fabrication

Herein, polystyrene-based particles possessing nucleobases in polymer side chains were prepared and nucleobase groups were applied to the interfacial photocrosslinking as photoreactive groups for the first time for fabricating hollow/capsule particles.