Carbon-centered radicals are indispensable building blocks for modern synthetic chemistry. In recent years, visible light photoredox catalysis has become a promising avenue to access C-centered radicals from a broad array of latent functional groups, including boronic acids. Herein, we present an aqueous protocol wherein water features a starring role to help transform aliphatic, aromatic, and heteroaromatic boronic acids to C-centered radicals with a bioinspired flavin photocatalyst. These radicals are used to deliver a diverse pool of alkylated products, including three pharmaceutically relevant compounds, via open-shell conjugate addition to disparate Michael acceptors. The mechanism of the reaction is investigated by computational studies, deuterium labeling, radical-trapping experiments, and spectroscopic analysis.

Most peptide drugs contain non-proteinogenic amino acids (NPAAs), born out through extensive structure-activity relationship (SAR) studies using solid-phase peptide synthesis (SPPS). Synthetically laborious and expensive to manufacture, NPAAs also can...

Modifications in RNA are numerous (∼170) and in higher numbers compared to DNA (∼5) making the ability to sequence an RNA molecule to identify these modifications highly tenuous using next generation sequencing (NGS). The ability to immobilize an exoribonuclease enzyme, such as XRN1, to a solid support while maintaining its activity and capability to cleave both the canonical and modified ribonucleotides from an intact RNA molecule can be a viable approach for single-molecule RNA sequencing. In this study, we report an enzymatic reactor consisting of covalently attached XRN1 to a solid support as the groundwork for a novel RNA exosequencing technique. The covalent attachment of XRN1 to a plastic solid support was achieved using EDC/NHS coupling chemistry. Studies showed that the solid-phase digestion efficiency of model RNAs was 87.6 ± 2.8%, while the XRN1 solution-phase digestion for the same model was 78.3 ± 4.4%. The ability of immobilized XRN1 to digest methylated RNA containing m6A and m5C ribonucleotides was also demonstrated. The processivity and clipping rate of immobilized XRN1 secured using single-molecule fluorescence measurements of a single RNA transcript demonstrated a clipping rate of 26 ± 5 nt s−1 and a processivity of >10.5 kb at 25°C.

Exchanging the ribose backbone of an oligonucleotide for a peptide can enhance its physiologic stability and nucleic acid binding affinity. Ordinarily, the eneamino nitrogen atom of a nucleobase is fused to the side chain of a polypeptide through a new CÀ N bond. The discovery of CÀ C linked nucleobases in the human transcriptome reveals new opportunities for engineering nucleopeptides that replace the traditional CÀ N bond with a non-classical CÀ C bond, liberating a captive nitrogen atom and promoting new hydrogen bonding and π-stacking interactions. We report the first late-stage synthesis of CÀ C linked carba-nucleopeptides (cNPs) using aqueous Rhodamine B photoredox catalysis. We prepare brand-new cNPs in batch, in parallel, and in flow using three long-wavelength photochemical setups. We detail the mechanism of our reaction by experimental and computational studies and highlight the essential role of diisopropylethylamine as a bifurcated twoelectron reductant.