Uncovering the selection criteria for the emergence of multi-building-block replicators from dynamic combinatorial libraries.
A family of self-replicating macrocycles was developed using dynamic combinatorial chemistry. Replication is driven by self-assembly of the replicators into fibrils and relies critically on mechanically induced fibril fragmentation. Analysis of separate dynamic combinatorial libraries made from one of six peptide-functionalized building blocks of different hydrophobicity revealed two selection criteria that govern the emergence of replicators from these systems. First, the replicators need to have a critical macrocycle size that endows them with sufficient multivalency to enable their self-assembly into fibrils. Second, efficient replication occurs only for library members that are of low abundance in the absence of a replication pathway. This work has led to spontaneous emergence of replicators with unrivalled structural complexity, being built from up to eight identical subunits and reaching a MW of up to 5.6 kDa. The insights obtained in this work provide valuable guidance that should facilitate future discovery of new complex self-replicating molecules. They may also assist in the development of new self-synthesizing materials, where self-assembly drives the synthesis of the very molecules that self-assemble. To illustrate the potential of this concept, the present system enables access to self-assembling materials made from self-synthesizing macrocycles with tunable ring size ranging from trimers to octamers.
Centre for Systems Chemistry, Stratingh Institute, University of Groningen , Nijenborgh 4, 9747 AG Groningen, The Netherlands.
Morteza
M
Malakoutikhah
Jérôme J-P
JJ
Peyralans
Mathieu
M
Colomb-Delsuc
Hugo
H
Fanlo-Virgós
Marc C A
MC
Stuart
Sijbren
S
Otto
D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry
D010455:Peptides