Peptide and Protein Building Blocks for Synthetic Biology: From Programming Biomolecules to Self-Organized Biomolecular Systems

Abstract

There are several approaches to creating synthetic-biological systems. Here, we describe a molecular-design approach. First, we lay out a possible synthetic-biology space, which we define with a plot of complexity of components versus divergence from nature. In this scheme, there are basic units, which range from natural amino acids to totally synthetic small molecules. These are linked together to form programmable tectons, for example, amphipathic alpha-helices. In turn, tectons can interact to give self-assembled units, which can combine and organize further to produce functional assemblies and systems. To illustrate one path through this vast landscape, we focus on protein engineering and design. We describe how, for certain protein-folding motifs, polypeptide chains can be instructed to fold. These folds can be combined to give structured complexes, and function can be incorporated through computational design. Finally, we describe how protein-based systems may be encapsulated to control and investigate their functions.

Structural specificity in coiled-coil interactions

“…Interest in coiled coils is heightened by their prevalence in biology, and by their potential applications in materials science and synthetic biology [7,8]. Coiled coils are predicted in ~10% of all eukaryotic proteins and are associated with widely ranging functions [9][10][11].…”

Supramolecular Principles of Self-Assembly of Pophyrin Nanotubes. 1. Models of SWPNTs Based on 5,10,15,20-Tetrakis(4’-sulfophenyl)porphine Zwitter-Ion

“…[1] The self-assembly strategy utilized by natural compounds is based on cooperative intermolecular interactions, it became a basis for a biomimetic approach towards new materials via "bottom-up" technology. In the past decade, researchers' attention towards studies of selfassembly processes has been exponentially increasing, as understanding this strategy is greatly promising for the design of various functional nano-materials such as molecular switches, luminescent probes, photonic bandgaps and catalysts.…”

An α‐Helix‐Mimicking 12,13‐Helix: Designed α/β/γ‐Foldamers as Selective Inhibitors of Protein–Protein Interactions

“…[1][2][3][4] As bioinspired structures,s ome of them have been validated as useful reagents to modulate (therapeutically important) biological processes and systems, [4][5][6][7][8][9] and others as building blocks for use in synthetic biology [10][11][12][13][14] or the construction of functional materials. [15,16] Ap articularly fertile area is centred on the search for foldamers that mimic natural secondary structures (specifically a-helices) and thereby act as inhibitors of protein-protein interactions (PPIs).…”