Talks & Lectures
17 Sep 2021
Virtual Event - Link Below

Asymmetric Lactam Synthesis with a Monomeric Streptavidin Artificial Metalloenzyme

Department of Chemistry and Chemical Biology

photo of Isra Hassan

Abstract

Reliable design of artificial metalloenzymes (ArMs) to access transformations not observed in nature remains a long-standing and important challenge. We report that a monomeric streptavidin (mSav) Rh(III) ArM permits asymmetric synthesis of α,β-unsaturated-δ-lactams via a tandem C-H activation and [4+2] annulation reaction. These products are readily derivatized to enantioenriched piperidines, the most common N-heterocycle found in FDA approved pharmaceuticals. Embedding a Rh cyclopentadienyl (Cp*) catalyst in the active site of mSav results in improved stereocontrol and a seven-fold enhancement in reactivity relative to the isolated biotinylated Rh(III) cofactor. With the goal of using protein engineering to improve the activity of monomeric streptavidin (mSav) ArM complexed to Rh(III), we also report computational calculations that demonstrate the effects of modifying the secondary coordination sphere. These findings have allowed us to engineer a more active mutant G49A that provides up to 67 more TON compared to WT mSavArM. Directed evolution techniques, when applied to ArMs, allows us to mimic the natural selection process and thereby dramatically increase the TON of the ArM. This technology has been used to develop an artificial aminobrominase with up to 2587 TON.

Biography

Isra Hassan completed her undergraduate studies at Stevens Institute of Technology under the mentorship of Professor AthulaAttygalle. She then went on to get her PhD in chemistry from Columbia University in the lab of Professor Tomislav Rovis. She now works at Novartis Institutes for Biomedical Research as a Chemical Biologist.

Join via Zoom: https://stevens.zoom.us/j/92933522177

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