Ultrasmall natural peptides self-assemble to strong temperature-resistant helical fibers in scaffolds suitable for tissue engineering

Mishra, Archana; Loo, Yihua; Deng, Rensheng; Chuah, Yon Jin; Hee, Hwan Tak; Ying, Jackie Y.; Hauser, Charlotte

doi:10.1016/j.nantod.2011.05.001

Cited by 107 publications

(130 citation statements)

References 17 publications

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“…There is a minimum critical concentration for each peptide below which no gelation is observed. Above the critical value, the speed of hydrogel formation followed the order LD 6 ≅ DF 5 > NL 6 > GA 6 > KE 7 > ID 3 , with the order LD 6 > ID 3 as previously observed (12,16). Formation of a solid gel was determined by visual inspection (turning the vial upside down).…”

Section: Resultsmentioning

confidence: 59%

“…Their origins and specific secondary structural transformations during self-assembly are also given. LD 6 (LIVAGD) and ID 3 (IVD) are two extensively characterized ultrasmall peptides (12,16), namely the bestperforming 6-mer with respect to propensity of gelation and gel strength, and a 3-mer. The natural core sequences include defined "hotspots" within amyloid proteins of high amyloidogenic potential, without and with one or two aromatic residues at different positions in the sequence (2, 5-8, 14, 17).…”

Section: Resultsmentioning

confidence: 99%

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Aliphatic peptides show similar self-assembly to amyloid core sequences, challenging the importance of aromatic interactions in amyloidosis

Lakshmanan

Cheong

Accardo

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

122

146

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The self-assembly of abnormally folded proteins into amyloid fibrils is a hallmark of many debilitating diseases, from Alzheimer's and Parkinson diseases to prion-related disorders and diabetes type II. However, the fundamental mechanism of amyloid aggregation remains poorly understood. Core sequences of four to seven amino acids within natural amyloid proteins that form toxic fibrils have been used to study amyloidogenesis. We recently reported a class of systematically designed ultrasmall peptides that self-assemble in water into cross-β-type fibers. Here we compare the self-assembly of these peptides with natural core sequences. These include core segments from Alzheimer's amyloid-β, human amylin, and calcitonin. We analyzed the self-assembly process using circular dichroism, electron microscopy, X-ray diffraction, rheology, and molecular dynamics simulations. We found that the designed aliphatic peptides exhibited a similar self-assembly mechanism to several natural sequences, with formation of α-helical intermediates being a common feature. Interestingly, the self-assembly of a second core sequence from amyloid-β, containing the diphenylalanine motif, was distinctly different from all other examined sequences. The diphenylalanine-containing sequence formed β-sheet aggregates without going through the α-helical intermediate step, giving a unique fiberdiffraction pattern and simulation structure. Based on these results, we propose a simplified aliphatic model system to study amyloidosis. Our results provide vital insight into the nature of early intermediates formed and suggest that aromatic interactions are not as important in amyloid formation as previously postulated. This information is necessary for developing therapeutic drugs that inhibit and control amyloid formation.

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Section: Resultsmentioning

confidence: 59%

Section: Resultsmentioning

confidence: 99%

Aliphatic peptides show similar self-assembly to amyloid core sequences, challenging the importance of aromatic interactions in amyloidosis

Lakshmanan

Cheong

Accardo

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

122

146

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“…Due to their small size these peptides are attractive, since they offer a cheap production alternative to other protein or peptide-based structures with longer sequences. 106,164 In a recent study, 165 the integrin-recognition motif RGD was conjugated to the hexamer peptide Ac-LIVAGKC (LK 6 C) and afterwards cysteine-mediated disulfide bonds were introduced to the nanofibers assembled from the hexamer. The bioactive RGD motif visibly supported (e) Transmission electron microscopy and (f) atomic force microscopy images of reduced graphene dispersions at pH 2 with a 1 : 8 graphene-amyloid fibril ratio demonstrating the formation of stable amyloid-graphene films that can remain conjugated and stable for several weeks.…”

Section: -151mentioning

confidence: 99%

“…All peptides of this class do not correspond to any known sequence of a natural protein, but were rationally designed. 118,164 Other peptide systems that adopt typical beta-sheet structures have been developed, for example by J. Collier, A. Aggelli, D. Pochan and others, discussed in a recent review. 36 …”

Section: Predicting Amyloid Propensity and Peptide Designmentioning

confidence: 99%

Amyloid-based nanosensors and nanodevices

2014

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Self-assembling amyloid-like peptides and proteins give rise to promising biomaterials with potential applications in many fields. Amyloid structures are formed by the process of molecular recognition and self-assembly, wherein a peptide or protein monomer spontaneously self-associates into dimers and oligomers and subsequently into supramolecular aggregates, finally resulting in condensed fibrils. Mature amyloid fibrils possess a quasi-crystalline structure featuring a characteristic fiber diffraction pattern and have well-defined properties, in contrast to many amorphous protein aggregates that arise when proteins misfold. Core sequences of four to seven amino acids have been identified within natural amyloid proteins. They are capable to form amyloid fibers and fibrils and have been used as amyloid model structures, simplifying the investigations on amyloid structures due to their small size. Recent studies have highlighted the use of self-assembled amyloid-based fibers as nanomaterials. Here, we discuss the latest advances and the major challenges in developing amyloids for future applications in nanotechnology and nanomedicine, with the focus on development of sensors to study protein-ligand interactions.

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“…Therefore, the main applications of SAPs have been in nanotechnology fields such as biomedical nanotechnology (13,14), molecular electronics (15), and cell culturing. In addition, SAPs can be used to protect membrane proteins (16,17) and improve the water solubility of plant cytochrome CYP73A1 (18).…”

mentioning

confidence: 99%

Fusion of Self-Assembling Amphipathic Oligopeptides with Cyclodextrin Glycosyltransferase Improves 2- O - d -Glucopyranosyl- l -Ascorbic Acid Synthesis with Soluble Starch as the Glycosyl Donor

Han

Shin

et al. 2014

Appl Environ Microbiol

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In this study, we fused six self-assembling amphipathic peptides (SAPs) with cyclodextrin glycosyltransferase (CGTase) from Paenibacillus macerans to catalyze 2-O-D-glucopyranosyl-L-ascorbic acid (AA-2G) production with cheap substrates, including maltose, maltodextrin, and soluble starch as glycosyl donors. The results showed that two fusion enzymes, SAP5-CGTase and SAP6-CGTase, increased AA-2G yields to 2.33-and 3.36-fold that of wild-type CGTase when soluble starch was used as a substrate. The cyclization activities of these enzymes decreased, while disproportionation activities increased. Enzymatic characterization of the two fusion enzymes was performed, and kinetics analysis of AA-2G synthesis confirmed the enhanced soluble starch specificity of SAP5-CGTase and SAP6-CGTase compared to that in the wild-type CGTase. As revealed by structure modeling of the fusion and wild-type CGTases, enhanced substrate-binding capacity may result from the increased number of hydrogen bonds present after fusion. This study demonstrates an effective protein fusion approach to improving the substrate specificity of CGTase for AA-2G synthesis. Fusion enzymes, especially SAP6-CGTase, are promising starting points for further development through protein engineering.

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Ultrasmall natural peptides self-assemble to strong temperature-resistant helical fibers in scaffolds suitable for tissue engineering

Cited by 107 publications

References 17 publications

Aliphatic peptides show similar self-assembly to amyloid core sequences, challenging the importance of aromatic interactions in amyloidosis

Aliphatic peptides show similar self-assembly to amyloid core sequences, challenging the importance of aromatic interactions in amyloidosis

Amyloid-based nanosensors and nanodevices

Fusion of Self-Assembling Amphipathic Oligopeptides with Cyclodextrin Glycosyltransferase Improves 2- O - d -Glucopyranosyl- l -Ascorbic Acid Synthesis with Soluble Starch as the Glycosyl Donor

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