Enzyme‐instructed self‐assembly of peptide derivatives to form nanofibers and hydrogels

Gao, Yuan; Yang, Zhimou; Kuang, Yi; Ma, Manlung; Li, Jiayang; Zhao, Fan; Xu, Bing

doi:10.1002/bip.21321

Cited by 104 publications

(85 citation statements)

References 78 publications

(91 reference statements)

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“…The Dex-PA nanofiber gels could therefore be useful to deliver a low and consistent dose of Dex for prolonged times, and indicates that these materials could have the release profile necessary for long-term localized anti-inflammatory activity. This strategy to use a hydrazone to control drug release kinetics could also be amenable to incorporation into the molecular design and solid-phase synthesis of many other classes of self-assembling peptide gelators [41, 67–69]. …”

Section: Resultsmentioning

confidence: 99%

Controlled release of dexamethasone from peptide nanofiber gels to modulate inflammatory response

et al. 2012

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New biomaterials that have the ability to locally suppress an immune response could have broad therapeutic use in the treatment of diseases characterized by acute or chronic inflammation or as a strategy to facilitate improved efficacy in cell or tissue transplantation. We report here on the preparation of a modular peptide amphiphile (PA) capable of releasing an anti-inflammatory drug, dexamethasone (Dex), by conjugation via a labile hydrazone linkage. This molecule self-assembled in water into long supramolecular nanofibers when mixed with a similar PA lacking the drug conjugate, and the addition of calcium salt to screen electrostatic repulsion between nanofibers promoted gel formation. These nanofiber gels demonstrated sustained release of soluble Dex for over one month in physiologic media. The Dex released from these gels maintained its anti-inflammatory activity when evaluated in vitro using a human inflammatory reporter cell line and furthermore preserved cardiomyocytes viability upon induced oxidative stress. The ability of this gel to mitigate the inflammatory response in cell transplantation strategies was evaluated using cell-surrogate polystyrene microparticles suspended in the nanofiber gel that were then subcutaneously injected in a mouse. Live animal luminescence imaging using the chemiluminescent reporter molecule luminol showed a significant reduction in inflammation at the site where particles were injected with Dex-PA compared to the site of injection for particles within a control PA in the same animal. Histological evidence suggested a marked reduction in the number of infiltrating inflammatory cells when particles were delivered within Dex-PA nanofiber gels and very little inflammation was observed at either 3 days or 21 days post-implantation. The use of Dex-PA could facilitate localized anti-inflammatory activity as a component of biomaterials designed for various applications in regenerative medicine and could specifically be a useful module for PA-based therapies. More broadly, these studies define a versatile strategy for facile synthesis of self-assembling peptide-based materials with the ability to control drug release.

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Section: Resultsmentioning

confidence: 99%

Controlled release of dexamethasone from peptide nanofiber gels to modulate inflammatory response

et al. 2012

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“…Self-assembly in living cells may also be crucial to create localized sites of specific enzymatic activity. For example, enzyme self-assembly is observed in vitro (Gao et al 2010) as well as in vivo (Noree et al 2010). Self-assembly may, therefore, control enzymatic activity depending on the metabolic status.…”

Section: Self-assembly Self-organization and Assisted Assembly In Tmentioning

confidence: 99%

Dynamic as well as stable protein interactions contribute to genome function and maintenance

Hemmerich

Schmiedeberg²,

Diekmann

2010

Chromosome Res

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The cell nucleus is responsible for the storage, expression, propagation, and maintenance of the genetic material it contains. Highly organized macromolecular complexes are required for these processes to occur faithfully in an extremely crowded nuclear environment. In addition to chromosome territories, the nucleus is characterized by the presence of nuclear substructures, such as the nuclear envelope, the nucleolus, and other nuclear bodies. Other smaller structural entities assemble on chromatin in response to required functions including RNA transcription, DNA replication, and DNA repair. Experiments in living cells over the last decade have revealed that many DNA binding proteins have very short residence times on chromatin. These observations have led to a model in which the assembly of nuclear macromolecular complexes is based on the transient binding of their components. While indeed most nuclear proteins are highly dynamic, we found after an extensive survey of the FRAP literature that an important subset of nuclear proteins shows either very slow turnover or complete immobility. These examples provide compelling evidence for the establishment of stable protein complexes in the nucleus over significant fractions of the cell cycle. Stable interactions in the nucleus may, therefore, contribute to the maintenance of genome integrity. Based on our compilation of FRAP data, we propose an extension of the existing model for nuclear organization which now incorporates stable interactions. Our new “induced stability” model suggests that self-organization, self-assembly, and assisted assembly contribute to nuclear architecture and function.Electronic supplementary materialThe online version of this article (doi:10.1007/s10577-010-9161-8) contains supplementary material, which is available to authorized users.

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“…Peptides can be driven to assemble into amyloid fibres or nanotubes upon activating switches that are modulated by physicochemical conditions (temperature and pH), [56] specific nucleobase hybridisation (in molecular chimeras between peptides and peptide-nucleic acids, PNAs), [57] metal (Zn 2 + , Cu 2 + ) coordination, [58] removal of fused modulator sequences by enzymatic (or photo-induced) O,N-acyl migration, [59] enzymatic phosphorylation/dephosphorylation [60] or chemical cross-linking. [61] A noteworthy example of the latter is the use of a fluorescent biarsenical and tetrathiolated ligand (FLAsH) to probe a-helical!b-sheet transformations and the relative orientations of b-strands in engineered tetracysteine mutants of amyloid proteins.…”

Section: Sequestrating Coupled Enzymatic Reactions Into Intracellularmentioning

confidence: 99%

Amyloid Assemblies: Protein Legos at a Crossroads in Bottom‐Up Synthetic Biology

Giraldo

2010

ChemBioChem

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One of the major objectives that bottom-up synthetic biology shares with chemical biology is to engineer extant biological molecules to implement novel functionalities in living systems. Proteins, due to their astonishing structural and functional versatility and to their central roles in the biology of cells, should be cornerstones of synthetic biology. In particular, protein amyloid cross-β assemblies constitute one of the most stable, conceptually simple and universal macromolecular architectures ever found in Nature and thus have enormous potential to be explored. This article focuses on the concepts behind the use of the amyloid cross-β-structural framework as a synthetic biology part, underlining recent basic findings and ideas. The pros and the cons associated with the polymorphism and the cellular toxicity of protein amyloids are also discussed, keeping in mind the possible suitability of these protein assemblies for scaffolding novel orthogonal macromolecular devices in vivo.

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Enzyme‐instructed self‐assembly of peptide derivatives to form nanofibers and hydrogels

Cited by 104 publications

References 78 publications

Controlled release of dexamethasone from peptide nanofiber gels to modulate inflammatory response

Controlled release of dexamethasone from peptide nanofiber gels to modulate inflammatory response

Dynamic as well as stable protein interactions contribute to genome function and maintenance

Amyloid Assemblies: Protein Legos at a Crossroads in Bottom‐Up Synthetic Biology

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