Expanding peptide diversity through selective chemistry and genetic code reprogramming

DRA lecture held by Associate Professor Seino Jongkees, Vrije Universiteit Amsterdam

Discovery of peptide hits by high throughput platforms relies on the right combination of diversity. Numerical diversity should be high, to assess as many candidates as possible, but also chemical diversity should be high to have as much difference as possible between those candidates. Genetically encoded platforms such as mRNA display do well in numerical diversity, but are limited in the chemical diversity of the building blocks that they can explore. Genetic code reprogramming can change (and slightly expand) the scope of building blocks that can be built into a peptide, but can also be used for introduction of reactive groups that enable subsequent chemical modification. We have been exploring how these two approaches, but especially chemical late stage modification/diversification, can be used on mRNA displayed peptides to expand the scope of what can be presented, using canonical and reprogrammed amino acids as reactive groups and addressing challenges such as diversifying macrocyclization approaches and introducing new functionality such as carbohydrates. With this we hope to address shortcomings such as peptide rigidity, stability, and targeting of specific binding sites.

The lecture is organised on behalf of the graduate programme in pharmaceutical sciences, Drug Research Academy, by Associate Professor Joseph Rogers, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen.

The DRA lecture is free of charge and open for attendance by all interested parties. It is not necessary to pre-register.