Elucidation of the Self-Assembly Pathway of Lanreotide Octapeptide into β-Sheet Nanotubes: Role of Two Stable Intermediates (original) (raw)
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Squaring the Circle in Peptide Assembly: From Fibers to Discrete Nanostructures by de Novo Design
Journal of the American Chemical Society, 2012
The design of bioinspired nanostructures and materials of defined size and shape is challenging as it pushes our understanding of biomolecular assembly to its limits. In such endeavors, DNA is the current building block of choice because of its predictable and programmable self-assembly. The use of peptide-and protein-based systems, however, has potential advantages due to their more-varied chemistries, structures and functions, and the prospects for recombinant production through gene synthesis and expression. Here, we present the design and characterization of two complementary peptides programmed to form a parallel heterodimeric coiled coil, which we use as the building blocks for larger, supramolecular assemblies. To achieve the latter, the two peptides are joined via peptidic linkers of variable lengths to produce a range of assemblies, from flexible fibers of indefinite length, through large colloidal-scale assemblies, down to closed and discrete nanoscale objects of defined stoichiometry. We posit that the different modes of assembly reflect the interplay between steric constraints imposed by short linkers and the bulk of the helices, and entropic factors that favor the formation of many smaller objects as the linker length is increased. This approach, and the resulting linear and proteinogenic polypeptides, represents a new route for constructing complex peptide-based assemblies and biomaterials.
Trends in Biotechnology, 2007
Self-assembly at the nanoscale is becoming increasingly important for the fabrication of novel supramolecular structures, with applications in the fields of nanobiotechnology and nanomedicine. Peptides represent the most favorable building blocks for the design and synthesis of nanostructures because they offer a great diversity of chemical and physical properties, they can be synthesized in large amounts, and can be modified and decorated with functional elements, which can be used in diverse applications. In this article, we review some of the most recent experimental advances in the use of nanoscale self-assembled peptide structures and the theoretical efforts aimed at understanding the microscopic determinants of their formation, stability and conformational properties. The combination of experimental observations and theoretical advances will be fundamental to fully realizing the biotechnological potential of peptide self-organization.
Control over Multiple Nano‐ and Secondary Structures in Peptide Self‐Assembly
Angewandte Chemie, 2021
Herein, we report the rich morphological and conformational versatility of a biologically active peptide (PEP-1), which follows diverse self-assembly pathways to form up to six distinct nanostructures and up to four different secondary structures through subtle modulation in pH, concentration and temperature. PEP-1 forms twisted b-sheet secondary structures and nanofibers at pH 7.4, which transform into fractal-like structures with strong b-sheet conformations at pH 13.0 or short disorganized elliptical aggregates at pH 5.5. Upon dilution at pH 7.4, the nanofibers with twisted bsheet secondary structural elements convert into nanoparticles with random coil conformations. Interestingly, these two selfassembled states at pH 7.4 and room temperature are kinetically controlled and undergo a further transformation into thermodynamically stable states upon thermal annealing: whereas the twisted b-sheet structures and corresponding nanofibers transform into 2D sheets with well-defined b-sheet domains, the nanoparticles with random coil structures convert into short nanorods with a-helix conformations. Notably, PEP-1 also showed high biocompatibility, low hemolytic activity and marked antibacterial activity, rendering our system a promising candidate for multiple bio-applications.
Self-assembly of protein derived peptides
2017
Self-assembling building blocks have become of increasing interest in the field of bionanotechnology due to their ability to self-assemble into defined geometrical shapes. Nature is abundant with examples of functional biological assemblies that are either rich in β-sheets or coiled coils. This research work investigates peptide sequences derived from simple protein interfaces, as molecular tectons for use in bionanotechnology. Protein interface sequences were chosen as a design source of peptide tectons, as they are naturally optimized to drive self-assembly in a highly controlled and regulated manner. This thesis work focused primarily on the simple β-continuous and the helical coiled coil protein interfaces. The peptide sequences designed from different protein-β interfaces all self-assembled into well-ordered nanostructures that were β-sheet rich and exhibited liquid crystallinity. SAXS and FTIR confirmed that the extended peptide nanostructures have the common architecture of β...
Rational design of peptide-based building blocks for nanoscience and synthetic biology
Faraday Discussions, 2009
The rational design of peptides that fold to form discrete nanoscale objects, and/ or self-assemble into nanostructured materials is an exciting challenge. Such efforts test and extend our understanding of sequence-to-structure relationships in proteins, and potentially provide materials for applications in bionanotechnology. Over the past decade or so, rules for the folding and assembly of one particular protein-structure motif-the a-helical coiled coilhave advanced sufficiently to allow the confident design of novel peptides that fold to prescribed structures. Coiled coils are based on interacting a-helices, and guide and cement many protein-protein interactions in nature. As such, they present excellent starting points for building complex objects and materials that span the nano-to-micron scales from the bottom up. Along with others, we have translated and extended our understanding of coiled-coil folding and assembly to develop novel peptide-based biomaterials. Herein, we outline briefly the rules for the folding and assembly of coiled-coil motifs, and describe how we have used them in de novo design of discrete nanoscale objects and soft synthetic biomaterials. Moreover, we describe how the approach can be extended to other small, independently folded protein motifs-such as zinc fingers and EF-handsthat could be incorporated into more complex, multi-component synthetic systems and new hybrid and responsive biomaterials.
The de novo design of α-helical peptides for supramolecular self-assembly
Current Opinion in Biotechnology, 2019
One approach to designing de novo proteinaceous assemblies and materials is to develop simple, standardised building blocks and then to combine these symmetrically to construct more-complex higher-order structures. This has been done extensively using -structured peptides to produce peptide fibres and hydrogels. Here we focus on building with de novo helical peptides. Because of their self-contained, well-defined structures and clear sequence-to-structure relationships, helices are highly programmable making them robust building blocks for biomolecular construction. The progress made with this approach over the past two decades is astonishing and has led to a variety of de novo assemblies, including discrete nanoscale objects, and fibrous, nanotube, sheet and colloidal materials. This body of work provides an exceptionally strong foundation for advancing the field beyond in vitro design and into in vivo applications including what we call protein design in cells.
Scientific reports, 2017
Enabling control over macromolecular ordering and the spatial distribution of structures formed via the mechanisms of molecular self-assembly is a challenge that could yield a range of new functional materials. In particular, using the self-assembly of minimalist peptides, to drive the incorporation of large complex molecules will allow a functionalization strategy for the next generation of biomaterial engineering. Here, for the first time, we show that co-assembly with increasing concentrations of a highly charged polysaccharide, fucoidan, the microscale ordering of Fmoc-FRGDF peptide fibrils and subsequent mechanical properties of the resultant hydrogel can be easily and effectively manipulated without disruption to the nanofibrillar structure of the assembly.
Fluidic-Directed Assembly of Aligned Oligopeptides with π-Conjugated Cores
Advanced Materials, 2013
Development of robust strategies for the engineered selfassembly of functional synthetic materials is a major challenge in advanced materials engineering. Biomimetic materials such as synthetic polypeptides and peptide-polymer conjugates serve as model systems that provide insight into the design and engineering of materials with predictable functional properties. Recent advances in synthetic bioorganic chemistry enabled increased control over residue profi le, chain length, and functional group placement, thereby facilitating self-assembly of synthetic biopolymers into complex architectures. However, the level of complexity of such structures has yet to match those attained by natural polymers (e.g., DNA and peptides) that deterministically self-assemble into functional, threedimensional hierarchical architectures. As a consequence, directed assembly techniques have emerged as potential new routes towards building supramolecular structures consisting of small molecules, oligomers, and polymers. Prior methods for fl uidic-directed assembly using laminar co-fl owing streams have shown promise in supramolecular assembly; however, simple laminar co-fl ows with uniform fl uid velocities preclude fi ne-scale control required for nanostructure alignment. In this work, we report the fl uidic-directed assembly of aligned supramolecular structures using planar extensional fl ow, which induces alignment of underlying material suprastructures due to its dominant extensional/compressional fl ow character. We demonstrate that microfl uidic-based assembly enables reproducible, reliable fabrication of aligned hierarchical constructs that do not form spontaneously in solution. In this way, fl uidic-directed assembly of supramolecular structures allows for unprecedented manipulation at the nano-and mesoscale, which has the potential to provide rapid and effi cient control of functional materials properties.
Self-assembly of peptides to nanostructures
Organic & Biomolecular Chemistry, 2014
The formation of well-ordered nanostructures through self-assembly of diverse organic and inorganic building blocks has drawn much attention owing to their potential applications in biology and chemistry.
In this tutorial review the process and applications of peptide self-assembly into nanotubes, nanospheres, nanofibrils, nanotapes, and other ordered structures at the nano-scale are discussed. The formation of well-ordered nanostructures by a process of self-association represents the essence of modern nanotechnology. Such self-assembled structures can be formed by a variety of building blocks, both organic and inorganic. Of the organic building blocks, peptides are among the most useful ones. Peptides possess the biocompatibility and chemical diversity that are found in proteins, yet they are much more stable and robust and can be readily synthesized on a large scale. Short peptides can spontaneously associate to form nanotubes, nanospheres, nanofibrils, nanotapes, and other ordered structures at the nano-scale. Peptides can also form macroscopic assemblies such as hydrogels with nano-scale order. The application of peptide building blocks in biosensors, tissue engineering, and the development of antibacterial agents has already been demonstrated.