Details

Autor(en) / Beteiligte

• Malakoutikhah, Morteza
• Peyralans, Jérôme J.-P
• Colomb-Delsuc, Mathieu
• Fanlo-Virgós, Hugo
• Stuart, Marc C. A
• Otto, Sijbren

Titel

Uncovering the Selection Criteria for the Emergence of Multi-Building-Block Replicators from Dynamic Combinatorial Libraries

Ist Teil von

• Journal of the American Chemical Society, 2013-12, Vol.135 (49), p.18406-18417

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.