Artificial Protein Block Copolymers Blocks Comprising Two Distinct Self-Assembling Domains (original) (raw)
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An Elastin-Derived Self-Assembling Polypeptide
Journal of Soft Matter, 2013
Elastin is an extracellular matrix protein responsible for the elastic properties of organs and tissues, the elastic properties being conferred to the protein by the presence of elastic fibers. In the perspective of producing tailor-made biomaterials of potential interest in nanotechnology and biotechnology fields, we report a study on an elastin-derived polypeptide. The choice of the polypeptide sequence encoded by exon 6 of Human Tropoelastin Gene is dictated by the peculiar sequence of the polypeptide. As a matter of fact, analogously to elastin, it is constituted of a hydrophobic region (GLGAFPAVTFPGALVPGG) and of a more hydrophilic region rich of lysine and alanine residues (VADAAAAYKAAKA). The role played by the two different regions in triggering the adoption of beta-turn and beta-sheet conformations is herein discussed and demonstrated to be crucial for the self-aggregation properties of the polypeptide.
Tuning self-assembly in elastin-derived peptides
Soft Matter, 2015
Elastin-derived peptides are gaining increasing interest as potential biomaterials. Previous studies have demonstrated that short elastin-derived peptides are able to self-assemble into fibrils as the entire elastin protein. The motif responsible for that is the XGGZG motif at least three-fold repeated. In this work we have synthesized and studied, at molecular and supramolecular levels, four pentadecapeptides obtained by switching the X and Z residue with leucine and/or valine. We found that the four peptides formed different supramolecular structures corresponding to specific molecular conformations. Our results show that not only the residue type but also the exact position occupied by the residue in the motif is crucial in driving the self-aggregation. The aim of this work is to provide the basis for designing elastinderived peptides with tunable supramolecular architecture. † Electronic supplementary information (ESI) available: Radius of gyration of peptides, 1 H-NMR chemical shi assignments of polypeptides, and CD of (VGGVG) 3 in TBS and in mixture TFE-H 2 O. See
Journal of biomedical materials research. Part A, 2017
We have recently developed a novel double-hydrophobic elastin-like triblock polypeptide called GPG, designed after the uneven distribution of two different hydrophobic domains found in elastin, an extracellular matrix protein providing elasticity and resilience to tissues. Upon temperature trigger, GPG undergoes a sequential self-assembling process to form flexible beaded nanofibers with high homogeneity and excellent dispersibility in water. Given that GPG might be a potential elastin-mimetic material, we sought to explore the biological activities of this block polypeptide. Besides GPG, several functionalized derivatives were also constructed by fusing functional motifs such as KAAK or KAAKGRGDS at the C-terminal of GPG. Although the added motifs affected the kinetics of fiber formation and β-sheet contents, all three GPGs assembled into beaded nanofibers at the physiological temperature. The resulting GPG nanofibers preserved their beaded structures in cell culture medium; theref...
Biomacromolecules, 2012
We report herein the unexpected temperature triggered self-assembly of proteins fused to thermally responsive elastin-like polypeptides (ELPs) into spherical micelles. Six ELP block copolymers (ELP BC ) with different hydrophilic and hydrophobic block lengths were genetically fused to two single domain proteins, thioredoxin (Trx) and a fibronectin type III domain (Fn3) that binds the α v β 3 integrin. The self-assembly of these protein-ELP BC fusions as a function of temperature was investigated by UV spectroscopy, light scattering, and cryo-TEM. Self-assembly of the ELP BC was -unexpectedly-retained upon fusion to the two proteins, resulting in the formation of spherical micelles with a hydrodynamic radius that ranged from 24-37 nm, depending on the protein and ELP BC . Cryo-TEM images confirmed the formation of spherical particles with a size that was consistent with that measured by light scattering. The bioactivity of Fn3 was retained when presented by the ELP BC micelles as indicated by the enhanced uptake of the Fn3-decorated ELP BC micelles in comparison to the unimer by cells that overexpress the α v β 3 integrin. The fusion of single domain proteins to ELP BC s may provide a ubiquitous platform for the multivalent presentation of proteins.
Elastin-mimetic protein polymers capable of physical and chemical crosslinking
Biomaterials, 2009
We report the synthesis of a new class of recombinant elastin-mimetic triblock copolymer capable of both physical and chemical crosslinking. These investigations were motivated by a desire to capture features unique to both physical and chemical crosslinking schemes so as to exert optimal control over a wide range of potential properties afforded by protein-based mutiblock materials. We postulated that by chemically locking a multiblock protein assembly in place, functional responses that are linked to specific domain structures and morphologies may be preserved over a broader range of loading conditions that would otherwise disrupt microphase structure solely stabilized by physical crosslinking. Specifically, elastic modulus was enhanced and creep strain reduced through the addition of chemical crosslinking sites. Additionally, we have demonstrated excellent in vivo biocompatibility of glutaraldehyde treated multiblock systems.
Elastin-like polypeptides as a promising family of genetically-engineered protein based polymers
World Journal of Microbiology and Biotechnology, 2014
Elastin-like polypeptides (ELP) are artificial, genetically encodable biopolymers, belonging to elastomeric proteins, which are widespread in a wide range of living organisms. They are composed of a repeating pentapeptide sequence Val-Pro-Gly-Xaa-Gly, where the guest residue (Xaa) can be any naturally occurring amino acid except proline. These polymers undergo reversible phase transition that can be triggered by various environmental stimuli, such as temperature, pH or ionic strength. This behavior depends greatly on the molecular weight, concentration of ELP in the solution and composition of the amino acids constituting ELPs. At a temperature below the inverse transition temperature (T t), ELPs are soluble, but insoluble when the temperature exceeds T t. Furthermore, this feature is retained even when ELP is fused to the protein of interest. These unique properties make ELP very useful for a wide variety of biomedical applications (e.g. protein purification, drug delivery etc.) and it can be expected that smart biopolymers will play a significant role in the development of most new materials and technologies. Here we present the structure and properties of thermally responsive elastin-like polypeptides with a particular emphasis on biomedical and biotechnological application.
Molecular Determinants for the Self-Assembly of Elastin Peptides
Conference Papers in Science, 2014
Elastin and elastin-related peptides have great potential in the biomaterial field, because of their peculiar mechanical properties and spontaneous self-assembling behavior. Depending on their sequences and under appropriate experimental conditions, they are able to self-assemble in different fiber morphologies, including amyloid-like fibers. In this work, we will review recent data on elastin peptides derived from exon 30-coded domain of human tropoelastin. This domain has been shown to be fundamental for the correct assembly of elastin. However, the N-terminal region forms amyloid-like fibers, while the C-terminal fragment forms elastin-like fibers. A rationale for the varied aggregation pattern has been sought in the molecular structure of the peptides. Minimal differences in the sequences, adopting alternative conformations, are shown to be responsible for the observed data.
Macromolecular Bioscience, 2007
Short polypeptides with four pentad repeats, (VPGVG)(4) and (VPAVG)(4), were synthesised by manual fluorenylmethoxycarbonyl/tert-butyl (Fmoc/t-Bu) solid phase peptide synthesis using a convergent approach. In the next step, the peptides were coupled via their N-terminus with activated semi-telechelic poly(ethylene glycol) O-(N-Fmoc-2-aminoethyl)-O'-(2-carboxyethyl)undeca(ethylene glycol) (Fmoc-PEG-COOH) to yield monodisperse Fmoc-PEG-peptide diblock copolymer. Both the presence of the terminal hydrophobic Fmoc group and the hydrophilic PEG chain in the copolymers were shown to play a crucial role in their self-associative behaviour, leading to reversible formation of supramolecular thermoresponsive assemblies. The peptides and their PEG derivatives were characterised by HPLC, NMR and MALDI-TOF MS. The associative behaviour of the peptides and their PEG derivatives was studied by dynamic light scattering, MAS NMR and phase contrast microscopy. [image: see text]