KPT330 improves Cas9 precision genome- and base-editing by selectively regulating mRNA nuclear export.

CRISPR-based genome engineering tools are associated with off-target effects that constitutively active Cas9 protein may instigate. Previous studies have revealed the feasibility of modulating Cas9-based genome- and base-editing tools using protein or small-molecule CRISPR inhibitors. Here we screened a set of small molecule compounds with irreversible warhead, aiming to identifying small-molecule modulators of CRISPR-Cas9.

Modular click chemistry libraries for functional screens using a diazotizing reagent.

Click chemistry is a concept in which modular synthesis is used to rapidly find new molecules with desirable properties. Copper(I)-catalysed azide-alkyne cycloaddition (CuAAC) triazole annulation and sulfur(VI) fluoride exchange (SuFEx) catalysis are widely regarded as click reactions, providing rapid access to their products in yields approaching 100% while being largely orthogonal to other reactions. However, in the case of CuAAC reactions, the availability of azide reagents is limited owing to their potential toxicity and the risk of explosion involved in their preparation.

Novel Approaches to Access Arylfluorosulfates and Sulfamoyl Fluorides Based on Sulfur (VI) Fluoride Exchange.

Sulfur (VI) fluoride exchange (SuFEx) is a new family of click chemistry reactions that relies on readily available sulfuryl fluoride (SO F ) and ethenesulfonyl fluoride to build diverse chemical structures bearing the S -F motif, such as fluorosulfate (-OSO F) and sulfonyl fluoride (-SO F). These motifs could be useful functional groups and connective linkers in organic synthesis. This unit describes two protocols for performing SuFEx.

A New Portal to SuFEx Click Chemistry: A Stable Fluorosulfuryl Imidazolium Salt Emerging as an "F-SO +" Donor of Unprecedented Reactivity, Selectivity, and Scope.

Sulfuryl fluoride, SO F , has been found to derivatize phenols in all kinds of environments, even those in highly functional molecules. We now report that a solid fluorosulfuryl imidazolium triflate salt delivers the same "F-SO +" fragment to Nu-H acceptor groups in the substrates. However, this triflate salt is a far more reactive fluorosulfurylating agent than SO F and displays selectivity preferences of its own.