Kalina Peneva

Max Planck Institute for Polymer Research, Mayence, Rheinland-Pfalz, Germany

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Publications (32)132.84 Total impact

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    ABSTRACT: Biophysical studies of the interaction of peptides with model membranes provide a simple yet effective approach to understand the transport of peptides and peptide based drug carriers across the cell membrane. Herein, the authors discuss the use of self-assembled monolayers fabricated from the full membrane-spanning thiol (FMST) 3-((14-((4'-((5-methyl-1-phenyl-35-(phytanyl)oxy-6,9,12,15,18,21,24,27,30,33,37-undecaoxa-2,3-dithiahenpentacontan-51-yl)oxy)-[1,1'-biphenyl]-4-yl)oxy)tetradecyl)oxy)-2-(phytanyl)oxy glycerol for ultrahigh vacuum (UHV) based experiments. UHV-based methods such as electron spectroscopy and mass spectrometry can provide important information about how peptides bind and interact with membranes, especially with the hydrophobic core of a lipid bilayer. Near-edge x-ray absorption fine structure spectra and x-ray photoelectron spectroscopy (XPS) data showed that FMST forms UHV-stable and ordered films on gold. XPS and time of flight secondary ion mass spectrometry depth profiles indicated that a proline-rich amphipathic cell-penetrating peptide, known as sweet arrow peptide is located at the outer perimeter of the model membrane.
    Biointerphases 03/2015; 10(1):019009. DOI:10.1116/1.4908164 · 2.68 Impact Factor
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    ABSTRACT: Electrophoretic deposition of colloidal nanoparticles shows great promise for the fabrication of nanostructured surfaces, especially relevant for the surface modification of three dimensional medical implants. Here, the role of small and bulky, chemisorbent and physisorbent ligands on metal (gold, platinum) nanoparticle deposition dynamics are systematically investigated. To be able to compare ligand-coated to ligand-free nanoparticles, pulsed laser ablation in liquid is employed as nanoparticle fabrication method. Nanoparticles’ electrophoretic properties are assessed via zeta potential measurements and nanoparticle tracking analysis, while online-UV–vis spectroscopy provides information about the deposition dynamics. Electron micrographs and contact angle measurements are employed to characterize the deposit. We show that ligand-free nanoparticles feature a high electrophoretic mobility and linear deposition kinetics, representing an excellent model material for controlled electrophoretic deposition. In contrast, the electrophoretic mobility of surface-modified nanoparticles is altered due to the surrounding ligand layer, resulting in less efficient deposition. Notably, electrophoretic mobility is not solely governed by the ligand's charge and does not correlate to the zeta potential values directly. Finally, bioactive nanotopographies with tunable wettability were created when depositing nanoparticles functionalized with cell-penetrating peptides. These peptide-nanoparticle bioconjugates have great potential to be used for mediating delivery via an implant surface such as a neural electrode.
    Applied Surface Science 02/2015; 348:92-99. DOI:10.1016/j.apsusc.2014.12.159 · 2.54 Impact Factor
  • Applied Surface Science 02/2015; · 2.54 Impact Factor
  • Ilja Tabujew, Marco Lelle, Kalina Peneva
    01/2015; DOI:10.1515/bnm-2015-0001
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    ABSTRACT: The search of targeted drug delivery systems requires the design of drug-carrier complexes, which could both reach the malignant cells and preserve the therapeutic substance activity. A promising strategy aimed at enhancing the uptake and reducing the systemic toxicity is to bind covalently the drug to a cell-penetrating peptide. For understanding the structure-activity relation in such preparations, the chemotherapeutic drug doxorubicin was investigated by unrestrained molecular dynamics simulations, supported by NMR, which yielded its molecular geometry in aqueous environment. Furthermore, the structure and dynamics of a conjugate of the drug with a cell-penetrating peptide was obtained from molecular dynamics simulations in aqueous solution. The geometries of the unbound compounds were characterized at different temperatures, the extent to which they change after covalent binding and whether/how they influence each other into the drug-peptide conjugate. The main structural fragments that affect the conformational ensemble of every molecule were found. The results show that the transitions between different substructures of the three compounds require modest amount of energy. At increased temperature either more conformations become populated as a result of the thermal fluctuations, or the relative shares of the various conformers equalize at the nanosecond scale. These frequent structural interconversions suggest expressed conformational freedom of the molecules. Conjugation into the drug-peptide compound partially immobilizes the molecules of the parent compounds. Nevertheless, flexibility still exists as well as an effective intra- and intermolecular hydrogen bonding that stabilizes the structures. We observe compact packing of the drug within the peptide that is also based on stacking interactions. All this outlines the drug-peptide conjugate as a prospective building block of a more complex drug-carrier system.
    The Journal of Physical Chemistry B 01/2015; 119(7). DOI:10.1021/jp509320q · 3.38 Impact Factor
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    Small 12/2014; · 7.51 Impact Factor
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    ABSTRACT: Colloidal particles with fluorescence read-out are commonly used as sensors for the quantitative determination of ions. Calcium, for example, is a biologically highly relevant ion in signaling, and thus knowledge of its spatio-temporal distribution inside cells would offer important experimental data. However, the use of particle-based intracellular sensors for ion detection is not straightforward. Important associated problems involve delivery and intracellular location of particle-based fluorophores, crosstalk of the fluorescence read-out with pH, and spectral overlap of the emission spectra of different fluorophores. These potential problems are outlined and discussed here with selected experimental examples. Potential solutions are discussed and form a guideline for particle-based intracellular imaging of ions. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Small 12/2014; 11(8). DOI:10.1002/smll.201402110 · 7.51 Impact Factor
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    ABSTRACT: Release of siRNA from nanoscale polyplexes is a crucial yet little investigated process, important during all stages of therapeutic research. Here we develop new methods to characterize polyplex stability early on in the development of new materials. We used double fluorescent labeled siRNA to compare binding and stability of a panel of chemically highly diverse nanoscale polyplexes, including peptides, lipids, nanohydrogels, poly-L-lysine brushes, HPMA block copolymers and manganese oxide particles. Conventional EMSA and heparin competition methods were contrasted with a newly developed microscale thermophoresis (MST) assay, a near-equilibrium method that allows free choice of buffer conditions. Integrity of FRET-labeled siRNA was monitored in the presence of nucleases, in cell culture medium and inside living cells. This approach characterizes all relevant steps from polyplex stability, over uptake to in vitro knockdown capability. Diverging polyplex binding properties revealed drawbacks of conventional EMSA and heparin competition assays, where MST and FRET-based siRNA integrity measurements offered a better discrimination of differential binding strength. Since cell culture medium left siRNA in all polyplexes essentially intact, the relevant degradation events could be pinpointed to occur inside cells. Differential binding strength of the variegated polyplexes correlated only partially with intracellular degradation. The most successful compounds in RNAi showed intermediate binding strength in our assays. We introduce new methods for the efficient and informative characterization of siRNA polyplexes with special attention to stability. Comparing FRET-labeled siRNA in different polyplexes associates successful knockdown with intermediate siRNA stability in various steps from formulation to intracellular persistence.
    Pharmaceutical Research 12/2014; 32(6). DOI:10.1007/s11095-014-1589-7 · 3.95 Impact Factor
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    ABSTRACT: In this study we describe the synthesis of novel functional non-nucleoside adenylyl cyclase inhibitors, which can be easily modified with thiol containing biomolecules such as tumour targeting structures. The linkage between inhibitor and biomolecule contains cleavable bonds to enable efficient intracellular delivery in the reductive milieu of the cytosol as well as in the acidic environment within endosomes and lysosomes. The suitability of this synthetic approach was shown by the successful bioconjugation of a poor cell permeable inhibitor with a cell penetrating peptide. Additionally, we have demonstrated the excellent inhibitory effect of the compounds presented here in a live-cell Förster resonance energy transfer-based assay in human embryonic kidney cells.This article is protected by copyright. All rights reserved.
    Chemical Biology &amp Drug Design 10/2014; 85(5). DOI:10.1111/cbdd.12452 · 2.51 Impact Factor
  • European Journal of Cancer 07/2014; 50:S207-S208. DOI:10.1016/S0959-8049(14)50755-1 · 4.82 Impact Factor
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    ABSTRACT: Here, the preparation of a novel block copolymer consisting of a statistical copolymer N-(2-hydroxypropyl) methacrylamide-s-N-(3-aminopropyl) methacrylamide and a short terminal 3-guanidinopropyl methacrylamide block is reported. This polymer structure forms neutral but water-soluble nanosized complexes with siRNA. The siRNA block copolymer complexes are first analyzed using agarose gel electrophoresis and their size is determined with fluorescence correlation spectroscopy. The protective properties of the polymer against RNA degradation are investigated by treating the siRNA block copolymer complexes with RNase V1. Heparin competition assays confirm the efficient release of the cargo in vitro. In addition, the utilization of microscale thermophoresis is demonstrated for the determination of the binding strength between a fluorescently labeled polyanion and a polymer molecule.
    Macromolecular Rapid Communications 07/2014; 35(13). DOI:10.1002/marc.201400120 · 4.61 Impact Factor
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    ABSTRACT: We report the first drug conjugate with a negatively charged amphipathic cell-penetrating peptide. Furthermore, we compare two different doxorubicin cell-penetrating peptide conjugates, which are both unique in their properties, due to their net charge at physiological pH, namely the positively charged octaarginine and the negatively charged proline-rich amphipathic peptide. These conjugates were prepared exploiting a novel heterobifunctional crosslinker to join the N-terminal cysteine residue of the peptides with the aliphatic ketone of doxorubicin. This small linker contains an activated thiol as well as aminooxy functionality, capable of generating a stable oxime bond with the C-13 carbonyl group of doxorubicin. The disulfide bond formed between the peptide and doxorubicin enables the release of the drug in the cytosol, as confirmed by drug-release studies performed in the presence of glutathione. Additionally, the cytotoxicity as well as the cellular uptake and distribution of this tripartite drug delivery system was investigated in MCF-7 and HT-29 cell lines. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.
    Journal of Peptide Science 05/2014; 20(5). DOI:10.1002/psc.2617 · 1.86 Impact Factor
  • Marco Lelle, Kalina Peneva
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    ABSTRACT: We describe the synthesis and characterization of a new lysine-based heterofunctional cross-linking reagent. It carries two readily available aminooxy functionalities and an activated and protected thiol group that is capable of generating reducible disulfides, the former enable bioorthogonal modification of ketones and aldehydes by the formation of an oxime bond. The efficacy of the linker was proven by coupling two doxorubicin molecules to the functionalized amino acid core and the subsequent bioconjugation of this drug conjugate with a thiolated antibody.
    Amino Acids 02/2014; DOI:10.1007/s00726-014-1685-3 · 3.65 Impact Factor
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    ABSTRACT: Polypeptides are successfully incorporated into poly(L-lactide) (PLLA) chains in a ring-opening polymerization (ROP) of L-lactide by using them as initiators. The resulting ABA triblock copolymers possess molecular weights up to 11000 g∙mol(-1) and polydispersities as low as 1.13, indicating the living character of the polymerization process. In a non-aqueous emulsion, peptide-initiated polymerization of L-lactide leads to well-defined nanoparticles, consisting of PLLA-block-peptide-block-PLLA copolymer. These nanoparticles are easily loaded by dye-encapsulation and transferred into aqueous media without aggregation (average diameter of 100 nm) or significant dye leakage. Finally, internalization of PLLA-block-peptide-block-PLLA nanoparticles by HeLa cells is demonstrated by a combination of coherent anti-Stokes Raman spectroscopy (CARS) and fluorescence microscopy. This demonstrates the promise of their utilization as cargo delivery vehicles.
    Biomacromolecules 03/2013; 14(5). DOI:10.1021/bm400216r · 5.79 Impact Factor
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    ABSTRACT: The two-dimensional diffusion of isolated molecular tracers at the water-n-alkane interface was studied with fluorescence correlation spectroscopy. The interfacial diffusion coefficients of larger tracers with a hydrodynamic radius of 4.0 nm agreed well with the values calculated from the macroscopic viscosities of the two bulk phases. However, for small molecule tracers with hydrodynamic radii of only 1.0 and 0.6 nm, notable deviations were observed, indicating the existence of an interfacial region with reduced effective viscosity and increased mobility.
    Physical Review E 01/2013; 87(1-1):012403. DOI:10.1103/PhysRevE.87.012403 · 2.33 Impact Factor
  • ChemInform 02/2011; 42(7). DOI:10.1002/chin.201107270
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    ABSTRACT: This Review summarizes the latest advances in the field of rylene dyes and rylene nanoemitters for applications in photonics, and describes the influence of the dye design on the optical properties, the self-assembly, the molecular interactions, as well as the labeling specificity of the compounds. The interplay between tailored (macro)molecular design and bulk/single-molecule spectroscopy enables complex processes to be explained, for example, the kinetics of energy-transfer processes or (bio)catalysis. Such investigations are essential for the ultimate design of optimized nanoemitters, and require a close cooperation between spectroscopists and preparative organic chemists.
    Angewandte Chemie International Edition 11/2010; 49(48):9068-93. DOI:10.1002/anie.200902532 · 11.34 Impact Factor
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    ABSTRACT: Dieser Aufsatz fasst die jüngsten Fortschritte auf dem Gebiet der Rylenfarbstoffe und Rylen-Nanoemitter für den Einsatz in der Photonik zusammen und beschreibt den Einfluss des Farbstoffdesigns auf die Leistungsmerkmale; im Zentrum stehen dabei die optischen Eigenschaften, die Selbstorganisation, die molekularen Wechselwirkungen sowie die Wechselwirkungsspezifität dieser Verbindungen. Die Messung ihrer Absorptions-, Emissions- oder Anregungsspektren ermöglicht die genaue Bestimmung der Position oder der dreidimensionalen Orientierung ihrer Übergangsdipolmomente. Wichtig ist hierbei das Wechselspiel zwischen maßgeschneidertem (makro)molekularem Design und Einzelmolekül-spektroskopischen Untersuchungen. Die experimentelle Verfolgung von Einzelmolekülen ermöglicht die Aufklärung komplexer Prozesse, z. B. der Kinetik von Energietransferprozessen oder der (Bio-)Katalyse, wodurch ein tieferes Verständnis der Entstehung und Herkunft von Unregelmäßigkeiten möglich wird. Derartige Untersuchungen sind für die Entwicklung verbesserter Nanoemitter unerlässlich und erfordern eine enge Zusammenarbeit von Spektroskopikern und Synthetikern.
    Angewandte Chemie 11/2010; 122(48). DOI:10.1002/ange.200902532
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    ABSTRACT: Employing the utility of the native chemical ligation, site-specific attachment of an ultrastable perylene dye to a derivative of the major light-harvesting complex (LHCII) was demonstrated. Biochemical analysis of the conjugate indicated that the structure and function of LHCII remain largely unaffected by the N-terminal modification.
    Organic & Biomolecular Chemistry 11/2010; 8(21):4823-6. DOI:10.1039/c0ob00492h · 3.49 Impact Factor
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    ABSTRACT: We monitored the action of phospholipase A(2) (PLA(2)) on L- and D-dipalmitoyl-phosphatidylcholine (DPPC) Langmuir monolayers by mounting a Langmuir-trough on a wide-field fluorescence microscope with single molecule sensitivity. This made it possible to directly visualize the activity and diffusion behavior of single PLA(2) molecules in a heterogeneous lipid environment during active hydrolysis. The experiments showed that enzyme molecules adsorbed and interacted almost exclusively with the fluid region of the DPPC monolayers. Domains of gel state L-DPPC were degraded exclusively from the gel-fluid interface where the buildup of negatively charged hydrolysis products, fatty acid salts, led to changes in the mobility of PLA(2). The mobility of individual enzymes on the monolayers was characterized by single particle tracking. Diffusion coefficients of enzymes adsorbed to the fluid interface were between 3.2 microm(2)/s on the L-DPPC and 4.9 microm(2)/s on the D-DPPC monolayers. In regions enriched with hydrolysis products, the diffusion dropped to approximately 0.2 microm(2)/s. In addition, slower normal and anomalous diffusion modes were seen at the L-DPPC gel domain boundaries where hydrolysis took place. The average residence times of the enzyme in the fluid regions of the monolayer and on the product domain were between approximately 30 and 220 ms. At the gel domains it was below the experimental time resolution, i.e., enzymes were simply reflected from the gel domains back into solution.
    Biophysical Journal 05/2010; 98(9):1873-82. DOI:10.1016/j.bpj.2010.01.035 · 3.83 Impact Factor