Ride the Tide: Novel NMR Approaches for Peptide Conformation and Kinetics Characterization
The interest in peptides as new scaffolds in the development of novel drugs has significantly increased owing to their potential to interact with novel and challenging biological targets. Nuclear magnetic resonance (NMR) has long been the method of choice for elucidating solution-state conformational ensembles and kinetics across diverse modalities, including peptides. Being an intrinsically quantitative analytical technique that delivers atomistic-level structural and dynamic information, NMR enables rapid peptide structural and conformational characterization. Furthermore, NMR data from mixture analysis can deliver comprehensive mechanistic insight and inform process development.
This presentation will introduce a recently developed NMR-based workflow for the rapid determination of high-resolution three-dimensional conformational ensembles of cyclic peptides and macrocycles in solution. The approach achieves accurate structures from a minimal set of NMR restraints by leveraging an advanced conformational sampling algorithm. In the second part, we will describe the development of a flow-NMR platform based on Bruker's InsightMR and associated methodologies that permit controlled modulation of sample conditions and real-time investigation of peptide kinetics. Together, these advances provide an integrated framework for multiscale structural analysis, offering rapid access to high-resolution solution conformations and assembly kinetics, with the potential to accelerate the design and development of novel peptide-based medicines.
What to Expect
This webinar presents advanced NMR methodologies for structural and kinetic characterization of cyclic peptides and macrocycles in solution. We will discuss workflows enabling high-resolution conformational ensembles from minimal restraints and introduce flow-NMR platforms for real-time kinetic analysis. These innovations provide a robust framework to accelerate peptide-based drug development.
Key Learning Points
- High-Resolution Conformational Ensembles
- Understand how minimal NMR restraints combined with advanced sampling algorithms enable accurate 3D structures of cyclic peptides and macrocycles.
- Real-Time Kinetic Analysis via Flow-NMR
- Explore methodologies for controlled modulation of sample conditions and dynamic monitoring of peptide assembly and kinetics.
- Integrated Framework for Drug Development
- Learn how these innovations accelerate peptide-based drug design by delivering atomistic insights into structure, dynamics, and mechanistic pathways.
Who Should Attend?
Structural biologists (NMR), medicinal and computational chemists, analytical and process development scientists, as well as anyone involved in peptide research, drug development, or structural analysis who wants to explore advanced NMR workflows for cyclic peptides and macrocycles.
Presenter: Mikhail Reibarkh (Senior Principal Scientist, Merck & Co., Inc.)
Mikhail Reibarkh is a scientific lead of the NMR group in the ARD department at Merck, where he works since 2009. He has a Ph.D. in Biophysics from the Moscow Institute of Physics and Technology, followed by postdocs at the University of Michigan and at Harvard Medical School. Prior to joining Merck, he worked at Varian, Inc.
Presenter: Qi Gao (Associate Principal Scientist, Merck & Co., Inc.)
Qi is an NMR spectroscopist at Merck, specializing in NMR-driven solutions for complex analytical challenges across small molecules, peptides, and biologics therapeutic development, with advanced structure elucidation and method innovation. Prior to joining Merck, she obtained her Ph.D. in Chemistry from the University of Georgia, focusing on glycoprotein characterization.
