Field of research
Living systems possess overwhelming molecular complexity that largely results from combinations of just twenty amino acids that are found across all life forms. It is increasingly clear that structure and functionality may be observed in much simpler combinations of amino acids in short peptides. Thus, beyond their role as the molecular building blocks of life, amino acids may be ideally suited as building blocks for adaptive nanotechnology. Most peptide assemblies have been discovered by chance or have been designed based on modification of known structures using an analytic or reductionist approach – a traditional chemical route in synthesis and analysis of isolated compounds, in which parts themselves cannot be analyzed any further.
Inspired by living systems, which they perform tasks that exceed the functionality of their basic constituents, the perspective shifted towards connectedness, interactivity and patterns. Systems chemistry focuses on mixtures of interacting molecules that continuously exchange chemical information, leading to emergent properties, properties that only originate when parts assemble together. This network concept contrasts with the aforementioned reductionist approach and has empowered peptide matter with the abilities to replicate, to compartmentalize and to adapt in response to chemical and physical signals from the environment. However, moving from molecules to dynamic molecular networks, akin to processes in living systems, we face the multifaceted challenge of spontaneous organization, autocatalysis, and active multicomponent assemblies, which can function by control of structure and time.
Systems chemistry is a powerful pathway towards the construction of adaptive and interactive chemical networks. Despite progress in the direction of chemically fueled systems, the manifestation and control of dynamics in these systems and the way they interact actively with biological entities remains a grand challenge. Unravelling the pathways that allow the spontaneous formation and destruction of peptide chemical networks by going beyond passive adaptation remain largely unanswered. The emission of chemical messengers, or physical counterstimuli, which in turn can trigger a secondary response, such as synchronization, co-development and learning has been limited only to polymeric systems.
The overall aim of this project is to develop spontaneous peptide chemical networks capable of dissipative adaptation and active communication with biological counterparts.
- By merging a chemically-activated pathway (activated esters) and catalytic self-assembly, the project will address a fundamental question in organic and supramolecular chemistry, which has been out for decades – formation and hydrolysis of amide bonds in water.
- This strategy will enable us to benefit from the rich chemistry of all the 20 natural amino acids but also expand towards hybrid and fully synthetic chemical systems which are linked with peptide bonds.
- Dissipative adaptation will be achieved through the use chemical (fuelling) and mechanical energy (audible sound waves).
- Using analytical techniques, we will develop a methodology to discover catalysts (amide formation and hydrolysis) and binders (DNA, sugars), which can dynamically alter the properties of such systems and offer non-equilibrium responses.
- Exposure to stimuli and counter-stimuli will empower peptide chemical networks with learning capabilities.
Top three publications
- Emergence of Low-Symmetry Foldamers from Single Monomers, C. G. Pappas, P. Mandal, B. Liu, B. Kauffmann, X. Miao, D. Komáromy, W. Hoffmann, C. Manz, R. Chang, K. Liu, K. Pagel, I. Huc and S. Otto, Nat. Chem., 2020, 12, 1180-1186.
- Dynamic peptide libraries for the discovery of supramolecular nanomaterials, C. G. Pappas, R. Shafi, I. R. Sasselli, H. Siccardi, T. Wang, V. Narang, R. Abzalimov, N. Wijerathne and R. V. Ulijn, Nat. Nanotechnol., 2016, 11, 960-967.
- Biocatalytic pathway selection in transient tripeptide nanostructures, C. G. Pappas, I. R. Sasselli and R. V. Ulijn, Angew. Chem. Int. Ed., 2015, 54, 8119-8123.