| 1. |
- Aili, Daniel, et al.
(author)
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Bioresponsive peptide-inorganic hybrid nanomaterials
- 2010
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In: Chemical Society Reviews. - : Royal Society of Chemistry. - 0306-0012 .- 1460-4744. ; 39:9, s. 3358-3370
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Research review (peer-reviewed)abstract
- Bioanalytical techniques that enable simple, fast and reliable high sensitivity monitoring of biomolecular interactions are of immense importance for diagnostics and drug development. This tutorial review provides an overview of recent progress in the development of peptide-based hybrid nanomaterials that transduce molecular interactions by exploiting the optical and magnetic properties of nanoparticles. Peptides have emerged as an interesting alternative to conventional biomolecular receptors, such as antibodies, and are facilitating the design of responsive hybrid nanomaterials that are both robust and sensitive for biodiagnostic applications.
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| 2. |
- Aili, Daniel, et al.
(author)
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Hybrid Nanoparticle-Liposome Detection of Phospholipase Activity
- 2011
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In: Nano letters (Print). - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 11:4, s. 1401-1405
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Journal article (peer-reviewed)abstract
- A flexible nanoparticle-based phospholipase (PL) assay is demonstrated in which the enzymatic substrate is decoupled from the nanoparticle surface. Liposomes are loaded with a polypeptide that is designed to heteroassociate with a second polypeptide immobilized on gold nanoparticies. Release of this polypeptide from the liposornes, triggered by PL, induces a folding-dependent nanoparticle bridging aggregation. The colorimetric response from this aggregation enables straightforward and continuous detection of PL in the picomolar range. The speed, specificity, and flexibility of this assay make it appropriate for a range of applications, from point of care diagnostics to high throughput pharmaceutical screening.
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| 3. |
- Aili, Daniel, et al.
(author)
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Polypeptide Folding-Mediated Tuning of the Optical and Structural Properties of Gold Nanoparticle Assemblies
- 2011
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In: Nano letters (Print). - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 11:12, s. 5564-5573
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Journal article (peer-reviewed)abstract
- Responsive hybrid nanomaterials with well-defined properties are of significant interest for the development of biosensors with additional applications in tissue engineering and drug delivery. Here, we present a detailed characterization using UV-vis spectroscopy and small angle X-ray scattering of a hybrid material comprised of polypeptide-decorated gold nanoparticles with highly controllable assembly properties. The assembly is triggered by a folding-dependent bridging of the particles mediated by the heteroassociation of immobilized helix-loop-helix polypeptides and a complementary nonlinear polypeptide present in solution. The polypeptides are de novo designed to associate and fold into a heterotrimeric complex comprised of two disulfide-linked four-helix bundles. The particles form structured assemblies with a highly defined interparticle gap (4.8 +/- 0.4 nm) that correlates to the size of the folded polypeptides. Transitions in particle aggregation dynamics, mass-fractal dimensions and ordering, as a function of particle size and the concentration of the bridging polypeptide, are observed; these have significant effects on the optical properties of the assemblies. The assembly and ordering of the particles are highly complex processes that are affected by a large number of variables including the number of polypeptides bridging the particles and the particle mobility within the aggregates. A fundamental understanding of these processes is of paramount interest for the development of novel hybrid nanomaterials with tunable structural and optical properties and for the optimization of nanoparticle-based colorimetric biodetection strategies.
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| 4. |
- Andrésen, Cecilia, et al.
(author)
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Critical biophysical properties in the Pseudomonas aeruginosa efflux gene regulator MexR are targeted by mutations conferring multidrug resistance
- 2010
-
In: Protein Science. - : Cold Spring Harbor Laboratory Press. - 0961-8368 .- 1469-896X. ; 19:4, s. 680-692
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Journal article (peer-reviewed)abstract
- The self-assembling MexA-MexB-OprM efflux pump system, encoded by the mexO operon, contributes to facile resistance of Pseudomonas aeruginosa by actively extruding multiple antimicrobials. MexR negatively regulates the mexO operon, comprising two adjacent MexR binding sites, and is as such highly targeted by mutations that confer multidrug resistance (MDR). To understand how MDR mutations impair MexR function, we studied MexR-wt as well as a selected set of MDR single mutants distant from the proposed DNA-binding helix. Although DNA affinity and MexA-MexB-OprM repression were both drastically impaired in the selected MexR-MDR mutants, MexR-wt bound its two binding sites in the mexO with high affinity as a dimer. In the MexR-MDR mutants, secondary structure content and oligomerization properties were very similar to MexR-wt despite their lack of DNA binding. Despite this, the MexR-MDR mutants showed highly varying stabilities compared with MexR-wt, suggesting disturbed critical interdomain contacts, because mutations in the DNA-binding domains affected the stability of the dimer region and vice versa. Furthermore, significant ANS binding to MexR-wt in both free and DNA-bound states, together with increased ANS binding in all studied mutants, suggest that a hydrophobic cavity in the dimer region already shown to be involved in regulatory binding is enlarged by MDR mutations. Taken together, we propose that the biophysical MexR properties that are targeted by MDR mutations stability, domain interactions, and internal hydrophobic surfaces are also critical for the regulation of MexR DNA binding.
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| 5. |
- Chen, Peng, et al.
(author)
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Peptide functionalized gold nanoparticles for colorimetric detection of matrilysin (MMP-7) activity
- 2013
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In: Nanoscale. - : Royal Society of Chemistry. - 2040-3364 .- 2040-3372. ; 5:19, s. 8973-8976
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Journal article (peer-reviewed)abstract
- A peptide with two cleavage sites for MMP-7 has been synthesized and immobilized on gold nanoparticles (AuNPs) through a cysteine residue. Digestion of the peptide by MMP-7 decreases its size and net charge, which leads to the aggregation of the AuNPs. The color shift caused by aggregation enables a direct and quantitative measurement of the concentration and activity of MMP-7 with an estimated limit of detection of 5 nM (0.1 μg mL−1).
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| 6. |
- de la Rica, Roberto, et al.
(author)
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Enzyme-responsive nanoparticles for drug release and diagnostics
- 2012
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In: Advanced Drug Delivery Reviews. - : Elsevier. - 0169-409X .- 1872-8294. ; 64:11, s. 967-978
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Research review (peer-reviewed)abstract
- Enzymes are key components of the bionanotechnology toolbox that possess exceptional biorecognition capabilities and outstanding catalytic properties. When combined with the unique physical properties of nanomaterials, the resulting enzyme-responsive nanoparticles can be designed to perform functions efficiently and with high specificity for the triggering stimulus. This powerful concept has been successfully applied to the fabrication of drug delivery schemes where the tissue of interest is targeted via release of cargo triggered by the biocatalytic action of an enzyme. Moreover, the chemical transformation of the carrier by the enzyme can also generate therapeutic molecules, therefore paving the way to design multimodal nanomedicines with synergistic effects. Dysregulation of enzymatic activity has been observed in a number of severe pathological conditions, and this observation is useful not only to program drug delivery in vivo but also to fabricate ultrasensitive sensors for diagnosing these diseases. In this review, several enzyme-responsive nanomaterials such as polymer-based nanoparticles, liposomes, gold nanoparticles and quantum dots are introduced, and the modulation of their physicochemical properties by enzymatic activity emphasized. When known, toxicological issues related to the utilization nanomaterials are highlighted. Key examples of enzyme-responsive nanomaterials for drug delivery and diagnostics are presented, classified by the type of effector biomolecule, including hydrolases such as proteases, lipases and glycosidases, and oxidoreductases.
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| 7. |
- Fyrner, Timmy, et al.
(author)
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Derivatization of a bioorthogonal protected trisaccharide linker : towards multimodal tools for chemical biology
- 2012
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In: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 23:6, s. 1333-1340
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Journal article (peer-reviewed)abstract
- When cross-linking biomolecules to surfaces or to other biomolecules, the use of appropriate spacer molecules is of great importance. Mimicking the naturally occurring spacer molecules will give further insight into their role and function, possibly unveil important issues regarding the importance of the specificity of carbohydrate-based anchor moieties, in e.g., glycoproteins and glycosylphosphatidylinositols. Herein, we present the synthesis of a lactoside-based trisaccharide, potentially suitable as a heterobifunctional bioorthogonal linker molecule whereon valuable chemical handles have been conjugated. An amino-derivative having thiol functionality shows promise as novel SPR-surfaces. Furthermore, the trisaccharide has been conjugated to a cholesterol moiety in combination with a fluorophore which successfully assemble on the cell surface in lipid microdomains, possibly lipid-rafts. Finally, a CuI-catalyzed azide-alkyne cycloaddition reaction (CuAAC) confirms the potential use of oligosaccharides as bioorthogonal linkers in chemical biology.
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| 8. |
- Fyrner, Timmy, et al.
(author)
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Synthesis of oligo(lactose)-based thiols and their self-assembly onto gold surfaces
- 2013
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In: Colloids and Surfaces B. - : Elsevier. - 0927-7765 .- 1873-4367. ; 105, s. 187-193
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Journal article (peer-reviewed)abstract
- The ability to produce monomolecular coatings with well-defined structural and functional properties is of key importance in biosensing, drug delivery, and many recently developed applications of nanotechnology. Organic chemistry has proven to be a powerful tool to achieve this in many research areas. Herein, we present the synthesis of three oligo(lactosides) glycosylated in a (1 → 3) manner, and which are further functionalized with amide-linked short alkanethiol spacers. The oligosaccharides (di-, tetra-, and hexasaccharide) originate from the inexpensive and readily available lactose disaccharide. These thiolated derivatives were immobilized onto gold surfaces, and the thus formed self-assembled monolayers (SAMs) on planar gold were characterized by wettability, ellipsometry and infrared reflection–absorption spectroscopy. Further, the ability of these SAMs to stabilize gold nanoparticles in saline solutions was also demonstrated, indicating that the oligosaccharides may be used as stabilizing agents in gold nanoparticle-based assays.
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| 9. |
- Hamedi, Mahiar, et al.
(author)
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Polypeptide-guided assembly of conducting polymer nanocomposites
- 2010
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In: NANOSCALE. - : Royal Society of Chemistry. - 2040-3364 .- 2040-3372. ; 2:10, s. 2058-2061
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Journal article (peer-reviewed)abstract
- A strategy for fabrication of electroactive nanocomposites with nanoscale organization, based on self-assembly, is reported. Gold nanoparticles are assembled by a polypeptide folding-dependent bridging. The polypeptides are further utilized to recruit and associate with a water soluble conducting polymer. The polymer is homogenously incorporated into the nanocomposite, forming conducting pathways which make the composite material highly conducting.
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| 10. |
- Hamedi, Mahiar, et al.
(author)
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Synthetic Polypeptides as Scaffolds for Supramolecular Assembly of Conducting Polymer Nanocomposites
- 2010
-
Other publication (other academic/artistic)abstract
- The development of nanoelectronics has resulted in enormous advancements in fabrication techniques that have enabled massproduction of CMOS circuits with feature sizes below 45nm. There is a large interest in new methods to further push the size limits, lower the production costs and to facilitate the design of more advanced three-dimensional structures beyond today’s 2.5 dimensional architectures. Self-assembly is probably the most important scheme in this development and is currently applied to many different areas and classes of nanoelectronics. Self-assembly enables fabrication of structures well below 10 nm in feature size and allows for incorporation of novel nanomaterials, such as metallic and semiconducting nanoparticles with many interesting optical and electrical properties. The controlled self-assembly of electro-active nanocomposites is of great interest for the development of novel functional materials including biosensors, electrochromic/plasmonic hybrid devices, and polymer/nanoparticle-based memories.
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