Primitive selection of the fittest emerging through functional synergy in nucleopeptide networks.

Many fundamental cellular and viral functions, including replication and translation, involve complex ensembles hosting synergistic activity between nucleic acids and proteins/peptides. There is ample evidence indicating that the chemical precursors of both nucleic acids and peptides could be efficiently formed in the prebiotic environment. Yet, studies on nonenzymatic replication, a central mechanism driving early chemical evolution, have focused largely on the activity of each class of these molecules separately. We show here that short nucleopeptide chimeras can replicate through autocatalytic and cross-catalytic processes, governed synergistically by the hybridization of the nucleobase motifs and the assembly propensity of the peptide segments. Unequal assembly-dependent replication induces clear selectivity toward the formation of a certain species within small networks of complementary nucleopeptides. The selectivity pattern may be influenced and indeed maximized to the point of almost extinction of the weakest replicator when the system is studied far from equilibrium and manipulated through changes in the physical (flow) and chemical (template and inhibition) conditions. We postulate that similar processes may have led to the emergence of the first functional nucleic-acid-peptide assemblies prior to the origin of life. Furthermore, spontaneous formation of related replicating complexes could potentially mark the initiation point for information transfer and rapid progression in complexity within primitive environments, which would have facilitated the development of a variety of functions found in extant biological assemblies.

Programmed Recognition between Complementary Dinucleolipids To Control the Self-Assembly of Lipidic Amphiphiles.

One of the major goals in systems chemistry is to create molecular assemblies with emergent properties that are characteristic of life. An interesting approach toward this goal is based on merging different biological building blocks into synthetic systems with properties arising from the combination of their molecular components. The covalent linkage of nucleic acids (or their constituents: nucleotides, nucleosides and nucleobases) with lipids in the same hybrid molecule leads, for example, to the so-called nucleolipids. Herein, we describe nucleolipids with a very short sequence of two nucleobases per lipid, which, in combination with hydrophobic effects promoted by the lipophilic chain, allow control of the self-assembly of lipidic amphiphiles to be achieved. The present work describes a spectroscopic and microscopy study of the structural features and dynamic self-assembly of dinucleolipids that contain adenine or thymine moieties, either pure or in mixtures. This approach leads to different self-assembled nanostructures, which include spherical, rectangular and fibrillar assemblies, as a function of the sequence of nucleobases and chiral effects of the nucleolipids involved. We also show evidence that the resulting architectures can encapsulate hydrophobic molecules, revealing their potential as drug delivery vehicles or as compartments to host interesting chemistries in their interior.