Protein CREATE enables closed-loop design of synthetic protein binders.

Proteins have proven to be useful agents in a variety of fields, from serving as potent therapeutics to enabling complex catalysis for chemical manufacture. However, they remain difficult to design and are instead typically selected for using extensive screens or directed evolution. Recent developments in protein large language models have enabled fast generation of diverse protein sequences in unexplored regions of protein space predicted to fold into varied structures, bind relevant targets, and catalyze novel reactions.

Chiral Acid-Catalyzed Atroposelective Indolization Enables Access to 1,1'-Indole-Pyrroles and Bisindoles Bearing a Chiral N-N Axis.

We present herein a highly atroposelective indolization for the efficient synthesis of 1,1'-biheteroaryls bearing a chiral N-N axis. Under the cooperative catalysis of chiral phosphoric acid and InBr, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. Derivatizations of these compounds to diverse functionalized N-N linked axially chiral biheteroaryls have also been demonstrated.