Title: "Mild Macrocyclization: New Chemoselective Strategies to Access Conformationally Constrained Peptides"

Victor Outlaw

University of Missouri

Host: Brett VanVeller

Abstract: Abstract. Although peptides are ideal candidates to modulate protein function and disrupt protein-protein interactions, their biological applications have been limited by low intracellular stability, poor cell permeability, and rapid in vivo clearance. Peptide macrocyclization has been shown to be an effective strategy for mitigating these unfavorable pharmacokinetic characteristics. The chemical diversity of macrocyclic peptides, however, is limited by the scarcity of orthogonal synthetic methods for chemoselective cyclization of peptides.

I will discuss my lab’s efforts to develop new orthogonal methods for peptide macrocyclization at tyrosine or lysine. These methods expand current capabilities by being (1) chemoselective, (2) operationally simple, and (3) progressing under mild and sustainable conditions. We exploit the chemoselective control of these methods for the synthesis of cyclic and stapled peptide analogs and demonstrate enhanced serum stability and bioactivity against a wide array of biological targets.

Bio: Victor K. Outlaw is an Assistant Professor of Chemistry at the University of Missouri whose research sits at the intersection of organic synthesis, chemical biology, and biophysics. His laboratory develops new synthetic methods, designs structurally defined peptides, and investigates the molecular interactions that underlie viral infection and other processes relevant to human health. 

Dr. Outlaw earned his B.S. in Chemistry from the University of Virginia and his Ph.D. from Johns Hopkins University, where he developed synthetic approaches to biologically relevant heterocyclic compounds. He subsequently completed NIH-funded postdoctoral research at the University of Wisconsin-Madison, where he worked on peptide-based antiviral therapeutics, including inhibitors of respiratory viruses and SARS-CoV-2. He joined the University of Missouri faculty in 2021. 

Combining tools from synthetic chemistry, structural biology, and biophysics, Dr. Outlaw's research aims to create new molecular architectures and therapeutic strategies while advancing our understanding of biologically important molecular interactions.

Outlaw Lab