Structure-Function Relationships in Dynamic Combinatorial Libraries

Abstract

The work carried out in this thesis provides examples on how variations in building block design affect self-assembly and self-replication behavior in dynamic combinatorial libraries. Chapter 1 provides an introduction in which possible definitions of life are discussed, together with the main characteristics of living systems (like self-replication and metabolism) and an overview of recent developments on self-replicators based on peptides and nucleobases. In Chapter 2 we report two peptide-based self-replicators that were utilized to synthesize supramolecular polymers with controllable size and composition. Our observations indicated that the nature of the polymers was strongly affected by the morphology of the sheared seeds. In Chapter 3 we show how self-replication can be tuned by the length of the spacer in DCLs made from two structurally different building blocks. In Chapter 4 we discovered parasitic behavior between self-replicators formed from building blocks that differ by a single methylene unit. We observed that a 6-ring replicator can only emerge when assisted by a pre-existing 8-ring self-replicator. Aiming for diversification of self-replicators through a cross-catalytic pathway under out-from-equilibrium conditions, we used continuous flow-set-ups in Chapter 5. First, we set up a system with two building blocks and optimized the experimental conditions in terms of flow rate, time and starting replicator composition. We also report attempts to create a cross-catalytic cycle by introducing a third building block. Finally, in Chapter 6, our studies are placed in a broader perspective and future prospects are discussed.