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CURATOR

Postdoctoral Scholar, University of California, San Diego

PINBOARD SUMMARY

Autocatalytic self-assembling peptides shed light on life’s chemical origins

Central role of self-replication

One of the essential features of life is self-reproduction, which occurs both on the molecular scale through the replication of genetic polymers (DNA, RNA), as well as larger scales through the reproduction of cells. While modern living organisms are extremely complex molecular assemblies that are the product of billions of years of evolution, there has been significant interest in developing simpler self-replicating systems.

Why autocatalysis?

Autocatalytic chemical reactions, whereby a molecule is able to catalyze its own formation, mimic nature’s ability to generate identical copies of relevant biomolecules. In particular, autocatalytic self-assembling peptides could be used as efficient building blocks for the construction of bioinspired nanomaterials, as well as for the study of the underlying mechanisms of self-association and principles that led to the first living systems on Earth.

Linking autocatalysis and self-assembly

My research is focused on the development of non-enzymatic and chemoselective methodologies capable of autocatalytically producing triskelion peptides that self-associate into spherical nanostructures. Serial transfer experiments demonstrate that autocatalysis successfully leads to continual self-assembly of three-dimensional nanospheres. Triskelion-based spherical architectures offer an opportunity to organize biomolecules and chemical reactions in unique, nanoscale compartments. Moreover, the ease with which the size and properties of autocatalytic peptide nanospheres can be controlled allows their use in fields such as biosensing, medicine and electronics. Peptide-based autocatalysts that are capable of self-assembly also represent a powerful tool for the construction of self-synthesizing biomaterials and may shed light on understanding life’s chemical origins and early evolution.

12 ITEMS PINNED

A chiroselective peptide replicator.

Abstract: The origin of homochirality in living systems is often attributed to the generation of enantiomeric differences in a pool of chiral prebiotic molecules, but none of the possible physiochemical processes considered can produce the significant imbalance required if homochiral biopolymers are to result from simple coupling of suitable precursor molecules. This implies a central role either for additional processes that can selectively amplify an initially minute enantiomeric difference in the starting material, or for a nonenzymatic process by which biopolymers undergo chiroselective molecular replication. Given that molecular self-replication and the capacity for selection are necessary conditions for the emergence of life, chiroselective replication of biopolymers seems a particularly attractive process for explaining homochirality in nature. Here we report that a 32-residue peptide replicator, designed according to our earlier principles, is capable of efficiently amplifying homochiral products from a racemic mixture of peptide fragments through a chiroselective autocatalytic cycle. The chiroselective amplification process discriminates between structures possessing even single stereochemical mutations within otherwise homochiral sequences. Moreover, the system exhibits a dynamic stereochemical 'editing' function; in contrast to the previously observed error correction, it makes use of heterochiral sequences that arise through uncatalysed background reactions to catalyse the production of the homochiral product. These results support the idea that self-replicating polypeptides could have played a key role in the origin of homochirality on Earth.

Pub.: 10 Mar '01, Pinned: 18 Oct '17

Toward self-constructing materials: a systems chemistry approach.

Abstract: To design the next generation of so-called "smart" materials, researchers will need to develop chemical systems that respond, adapt, and multitask. Because many of these features occur in living systems, we expect that such advanced artificial systems will be inspired by nature. In particular, these new materials should ultimately combine three key properties of life: metabolism, mutation, and self-replication. In this Account, we discuss our endeavors toward the design of such advanced functional materials. First, we focus on dynamic molecular libraries. These molecular and supramolecular chemical systems are based on mixtures of reversibly interacting molecules that are coupled within networks of thermodynamic equilibria. We will explain how the superimposition of combinatorial networks at different length scales of structural organization can provide valuable hierarchical dynamics for producing complex functional systems. In particular, our experimental results highlight why these libraries are of interest for the design of responsive materials and how their functional properties can be modulated by various chemical and physical stimuli. Then, we introduce examples in which these dynamic combinatorial systems can be coupled to kinetic feedback loops to produce self-replicating pathways that amplify a selected component from the equilibrated libraries. Finally, we discuss the discovery of highly functional self-replicating supramolecular assemblies that can transfer an electric signal in space and time. We show how these wires can be directly incorporated within an electronic nanocircuit by self-organization and functional feedback loops. Because the network topologies act as complex algorithms to process information, we present these systems in this order to provide context for their potential for extending the current generation of responsive materials. We propose a general description for a potential autonomous (self-constructing) material. Such a system should self-assemble among several possible molecular combinations in response to external information (input) and possibly self-replicate to amplify its structure. Ultimately, its functional response (output) can drive the self-assembly of the system and also serve a mechanism to transfer this initial information. Far from equilibrium, such synergistic processes could give rise to evolving, "information gaining" systems which become increasingly complex because internal self-organization rapidly reduces the potential energy surrounding the system.

Pub.: 27 Apr '12, Pinned: 18 Oct '17

Continual reproduction of self-assembling oligotriazole peptide nanomaterials.

Abstract: Autocatalytic chemical reactions, whereby a molecule is able to catalyze its own formation from a set of precursors, mimic nature's ability to generate identical copies of relevant biomolecules, and are thought to have been crucial for the origin of life. While several molecular autocatalysts have been previously reported, coupling autocatalytic behavior to macromolecular self-assembly has been challenging. Here, we report a non-enzymatic and chemoselective methodology capable of autocatalytically producing triskelion peptides that self-associate into spherical bioinspired nanostructures. Serial transfer experiments demonstrate that oligotriazole autocatalysis successfully leads to continual self-assembly of three-dimensional nanospheres. Triskelion-based spherical architectures offer an opportunity to organize biomolecules and chemical reactions in unique, nanoscale compartments. The use of peptide-based autocatalysts that are capable of self-assembly represents a promising method for the development of self-synthesizing biomaterials, and may shed light on understanding life's chemical origins.Molecules that act as both autocatalysts and material precursors offer exciting prospects for self-synthesizing materials. Here, the authors design a triazole peptide that self-replicates and then self-assembles into nanostructures, coupling autocatalytic and assembly pathways to realize a reproducing supramolecular system.

Pub.: 30 Sep '17, Pinned: 18 Oct '17