AbstractWith an interest in sustainable polymers derived from nucleoside building blocks, d-thymidine and carbon disulfide (CS2) were used as synthetic precursors to construct a trans-fused, 6,5-membered bicyclic xanthate, 3′,5′-cyclic N3-(3-butenyl)-d-thymidine trans xanthate, for ring-opening polymerization (ROP) to yield stereo- and regiochemically defined homopolymer analogs of nucleic acids bearing thiocarbonate backbones. Screenings for CS2 insertion and succeeding cyclization to form the targeted monomer revealed two additional d-thymidine-derived cyclic moieties, including a xanthate and trithiocarbonate of cis-fused configurations, isolated in low yields. Therefore, ROP experiments using alkoxy-based initiators and organobase catalysts at room temperature and supporting DFT calculations for enthalpies of ring opening were extended to all three potential monomers, with only the trans-fused bicyclic xanthate undergoing ROP. Structural characterization by MALDI-TOF mass spectrometry and NMR spectroscopy of polymers obtained from ROPs of 3′,5′-cyclic N3-(3-butenyl)-d-thymidine trans xanthate conducted at or somewhat below ambient temperatures indicated the presence of linear and cyclic species having primarily dimeric 5′,5′-trithiocarbonate-co-3′,3′-thionocarbonate connectivities from an alternating C–S and C–O cleavage pathway. Other minor trithiocarbonate, xanthate, and thionocarbonate functionalities were proposed to arise from backbiting reactions and/or minor regiorandom cleavages. In contrast, ROPs conducted at reduced temperatures (≤ −20 or −40 °C depending on the organobase) achieved selective C–S cleavage to yield 3′,5′-xanthate-connected polymers of N3-(3-butenyl)-d-thymidine with more structural similarity to native DNA. These fundamental advances extend the breadth of nucleoside-derived polymers, emphasizing the influence of sulfur incorporation during monomer synthesis and upon subsequent ROPs, with outcomes being temperature-mediated alternating vs. unidirectional backbone compositional and structural regioregularity.

Here, we performed two high-throughput methods established for detecting tRNA pseudouridylation positions: Nanopore direct RNA sequencing (DRS) and 2-bromoacrylamide-assisted cyclization sequencing (BACS).

A cascade photochemical cyclization strategy enables peripheral N-doped nanographenes with programmable monolayer and bilayer architectures. The bilayer assembly undergoes solvent-responsive dissociation in hydrogen-bond-accepting solvents. ABSTRACT Nitrogen-doped nanographenes (NGs) with precise structures are attractive because of their tunable electronic structures and supramolecular assembly behaviors. However, the synthesis of structurally diverse architectures, especially discrete bilayer systems, remains challenging. Herein, we report a cascade photo-induced radical cyclization (PIRC) strategy for the programmable synthesis of a series of peripheral nitrogen-doped NGs with tunable monolayer and bilayer architectures. Starting from nitrogen-doped nanographene 1 as a versatile structural platform, π-extension affords the larger monolayer nanographene 2, whereas modulation of the peripheral steric substituents enables the formation of a discrete bilayer assembly, (3)2. Single-crystal x-ray diffraction confirmed the monolayer structures of 1 and 2, while NMR spectroscopy, MALDI-TOF mass spectrometry, and DFT calculations revealed that (3)2 adopts a bilayer configuration. Compared with the monolayer analogues, the bilayer assembly shows broadened and blue-shifted absorption features characteristic of H-type coupling. More importantly, peripheral N─H functionalities enable solvent-responsive dissociation of the bilayer through hydrogen bonding with oxygen-containing solvents, leading to a solvent-switchable transformation between bilayer and monolayer states. The aggregation behavior of (3)2 is governed by the orthogonality between π–π interactions and hydrogen bonding, giving rise to a unique solvent-dependent yet concentration-independent structural transformation.

AbstractAmino aldehyde intermediates exhibit extreme chemical lability, undergoing nonproductive cyclization and polymerization in bulk solvent at rates or

The first chemically fueled small-molecule walker dances around a sugar molecule without falling off

The long-range RNA-RNA interaction between the termini of a flavivirus genome is controlled by multiple local RNA secondary and tertiary structures. However, a complete picture of this essential genome cyclization process is still elusive. Herein, by using selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE), SHAPE and mutational profiling, in vitro RNA binding assays, and reverse genetics approaches, we demonstrated that the hairpin 2 in the capsid-coding region (cHP2) is required for efficient replication of yellow fever virus and functionally interacts with the 3'-small hairpin (sHP) during genome cyclization. Interestingly, through a combination of multidimensional chemical probing and functional characterization assays, it was discovered that the sHP forms previously unknown tertiary interactions with an immediately upstream GACG region embedded within the 3'-cyclization sequence. This crucial tertiary RNA motif accounts for a potential negative regulatory mechanism of genome cyclization and is universally conserved among the mosquito-borne-related flaviviruses, which constitute a major phylogenetic branch within the subgenus Euflavivirus, genus Orthoflavivirus. Our study highlights the intricacy of RNA-based regulation in flaviviruses.

Read the full paper: Development of proteome-derived cyclic peptide libraries via ortho-phthalaldehyde-assisted cyclization

The long-range RNA-RNA interaction between the termini of a flavivirus genome is controlled by multiple local RNA secondary and tertiary structures. However, a complete picture of this essential genome cyclization process is still elusive. Herein, by using selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE), SHAPE and mutational profiling, in vitro RNA binding assays, and reverse genetics approaches, we demonstrated that the hairpin 2 in the capsid-coding region (cHP2) is required for efficient replication of yellow fever virus and functionally interacts with the 3'-small hairpin (sHP) during genome cyclization. Interestingly, through a combination of multidimensional chemical probing and functional characterization assays, it was discovered that the sHP forms previously unknown tertiary interactions with an immediately upstream GACG region embedded within the 3'-cyclization sequence. This crucial tertiary RNA motif accounts for a potential negative regulatory mechanism of genome cyclization and is universally conserved among the mosquito-borne-related flaviviruses, which constitute a major phylogenetic branch within the subgenus Euflavivirus, genus Orthoflavivirus. Our study highlights the intricacy of RNA-based regulation in flaviviruses.