Designing Three Dimensional Peptide Scaffolds

Organic Chemistry, Peptide Synthesis

The Roberts laboratory is motivated by the structural complexity achieved by nature to produce biologically active peptides. Our research aims to develop approaches to reproduce this complexity by constructing these structures using chemical and peptide synthesis tools. For example/lasso peptides are therapeutically relevant natural products of growing interest due to their unique three-dimensional shape that results when a circular ring becomes threaded with a linear segment that becomes locked in place by bulky groups that prevent its unthreading. To recreate these folded molecules/we are working to develop a nature-inspired approach. We first build amino acid reagents by chemical synthesis to enable reversible circularization. These reagents can then be incorporated into peptides grown on solid beads/one amino acid residue at a time/to control the order of building blocks that comprise the peptide sequence. Once built/these peptides are taken off the solid beads so they can be purified/reacted/and evaluated for their ability to fold into a lasso peptide. To guide our folding strategy/we are collaborating with the Swanson laboratory to understand and design improved lasso peptides folds using computational tools to refine the targets for evaluation. Skills developed: Fundamental laboratory skills/solid-phase peptide synthesis (SPPS)/purification and analysis by high-performance liquid chromatography (HPLC)/and structural analysis by mass spectrometry (MS). Scientific professional development: Critical thinking/communicating results/time management/and teamwork.

Stream Leaders

Andrew Roberts, PhD
Assistant Professor, Chemistry
Marcus Mifflin
Graduate Student Researcher