Leonard J. Prins

University of Padova, Padua, Veneto, Italy

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Publications (80)597.9 Total impact

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    Cristian Pezzato · Leonard J. Prins
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    ABSTRACT: A fundamental difference exists in the way signal generation is dealt with in natural and synthetic systems. While nature uses the transient activation of signalling pathways to regulate all cellular functions, chemists rely on sensory devices that convert the presence of an analyte into a steady output signal. The development of chemical systems that bear a closer analogy to living ones (that is, require energy for functioning, are transient in nature and operate out-of-equilibrium) requires a paradigm shift in the design of such systems. Here we report a straightforward strategy that enables transient signal generation in a self-assembled system and show that it can be used to mimic key features of natural signalling pathways, which are control over the output signal intensity and decay rate, the concentration-dependent activation of different signalling pathways and the transient downregulation of catalytic activity. Overall, the reported methodology provides temporal control over supramolecular processes.
    Nature Communications 07/2015; 6:7790. DOI:10.1038/ncomms8790 · 11.47 Impact Factor
  • ChemInform 07/2015; 46(30). DOI:10.1002/chin.201530330
  • Leonard J Prins
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    ABSTRACT: In many origin-of-life scenarios, inorganic materials, such as FeS or mineral clays, play an important role owing to their ability to concentrate and select small organic molecules on their surface and facilitate their chemical transformations into new molecules. However, considering that life is made up of organic matter, at a certain stage during the evolution the role of the inorganic material must have been taken over by organic molecules. How this exactly happened is unclear, and, indeed, a big gap separates the rudimentary level of organization involving inorganic materials and the complex organization of cells, which are the building blocks of life.
    Accounts of Chemical Research 06/2015; 48(7). DOI:10.1021/acs.accounts.5b00173 · 22.32 Impact Factor
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    ABSTRACT: In this review we describe the use of monolayer protected gold nanoparticles (Au NPs) for chemosensing applications. The attention is focused on a special subclass of Au NPs, namely those that contain binding sites for metal ions in the monolayer. It will be shown that these systems are very well-equipped for metal ion sensing as the complexation of the metal ions can affect the properties of the system in many ways leading towards detectable output signals even at very low analyte concentrations. In addition, the presence of metal ions in the monolayer themselves can serve as recognition units for the highly selective interaction with small organic molecules or biomacromolecules. Key examples will be discussed to underscore the attractive properties and potential of this class of Au NPs as components of chemosensing assays.
    Chemical Communications 04/2015; DOI:10.1039/C5CC00814J · 6.83 Impact Factor
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    Subhabrata Maiti · Leonard Jan Prins
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    ABSTRACT: Here, we show that the addition of Hg2+ or Ag+ metal ions to a dynamic system composed of monolayer protected gold nanoparticles (Au NPs) and a mixture of four nucleotides (dGMP, dAMP, TMP, and dCMP) leads to the self-selection of TMP or dGMP, respectively, on the monolayer surface.
    Chemical Communications 02/2015; 51(26). DOI:10.1039/C5CC01127B · 6.83 Impact Factor
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    ABSTRACT: A straightforward indicator-displacement assay (IDA) has been developed for the quantitative analysis of ATP→ADP conversion. The IDA relies on the use of gold nanoparticles passivated with a monolayer of thiols terminating with a 1,4,7-triazacyclononane (TACN)▪Zn2+ head group. The analytes ATP and ADP compete to a different extent with a fluorescent probe for binding to the monolayer surface. In the presence of ATP the fluorescent probe is free in solution, whereas in the presence of ADP the fluorescent probe is captured by the nanoparticles and its fluorescence is quenched. The linear response of the fluorescence signal towards different ratios of ATP : ADP permitted the detection of protein kinase activity simply by adding aliquots of the enzyme solution to the assay solution followed by measurement of the fluorescent intensity. The assay poses no restrictions on the target kinase nor does it require labeling of the kinase substrate. The assay was tested on the protein kinases PIM-1 and Src and validated through a direct comparison with the classical radiometric assay using [γ-32P]-labeled ATP.
    Organic & Biomolecular Chemistry 11/2014; 13(4). DOI:10.1039/C4OB02052A · 3.56 Impact Factor
  • Christian Franceschini · Paolo Scrimin · Leonard J Prins
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    ABSTRACT: The place-exchange reaction of thiol-containing peptides in a cationic monolayer on gold nanoparticles occurs very rapidly at low micromolar concentrations in water with excellent control over the degree of substitution. The driving force for this process is the binding of anionic peptides to a cationic monolayer surface which causes a strong increase in the local concentration of thiols. The place-exchange reaction can be triggered by light using a photolabile protecting group on the thiol moiety.
    Langmuir 10/2014; 30(46). DOI:10.1021/la5034965 · 4.46 Impact Factor
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    ABSTRACT: A self-assembled sensing system able to detect Hg(II) at low nanomolar concentrations is reported that operates through a signal transduction pathway that involves multivalent interactions. The analyte causes dimerization of low affinity ligands resulting in a complex with a high affinity for a multivalent monolayer protected gold nanoparticle. This complex displaces a quenched fluorescent reporter from the gold nanoparticle resulting in a turn ON of fluorescence. It is shown that the strength of the output signal can be regulated by tuning the multivalent interactions between the complex and the nanoparticle. Finally, it is shown that multivalent interactions drive the self-selection of a high-affinity complex from a mixture of low affinity ligands.
    Journal of the American Chemical Society 07/2014; 136(32). DOI:10.1021/ja506325e · 12.11 Impact Factor
  • Cristian Pezzato · Paolo Scrimin · Leonard J Prins
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    ABSTRACT: Herein, we describe the self-sorting of phosphate- and carboxylate-containing molecules on the surface of monolayer-protected gold nanoparticles. Self-sorting is driven by selective interactions between the phosphate probe and Zn(2+) complexes in one monolayer; these interactions force the carboxylate probe to move to a second type of nanoparticle. This process effectively separates the probes and causes their localization in well-defined spaces surrounding the nanoparticles. The removal/addition of Zn(2+) metal ions from the system is used to convert the system from an ordered to a disordered state and vice versa. The possibility to control the location and transport of populations of molecules in a complex mixture creates new perspectives for the development of innovative complex catalytic systems that mimic nature.
    Angewandte Chemie International Edition 02/2014; 53(8). DOI:10.1002/anie.201309747 · 11.26 Impact Factor
  • Leonard J Prins · Paolo Scrimin
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    ABSTRACT: Processive catalysis is frequent in nature, but much less common in synthetic systems. Now, a semisynthetic biohybrid catalytic system is reported that oxidizes DNA in a processive manner.
    Nature Chemistry 10/2013; 5(11):899-900. DOI:10.1038/nchem.1785 · 25.33 Impact Factor
  • Giulio Gasparini · Federico Rastrelli · Leonard J Prins
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    ABSTRACT: A protocol is described that permits the self-selection of hydrazides from a small library by a phosphonate-target immobilized on resin. Hydrazides are captured by a neighbouring aldehyde group through reversible hydrazone bond formation. Stabilizing intramolecular interactions between the phosphonate-target and functional groups of the hydrazides drive the selection process. The phosphonate-target is introduced onto commercially available Tentagel resin through straightforward synthetic steps. The functionalized resin could be conveniently characterized by HR-MAS NMR spectroscopy using a recently developed transverse relaxation filter that eliminates the strong phase defects commonly observed with CPMG sequences. In addition, a protocol was developed to quantitatively remove the captured hydrazides from resin in order to analyse their composition by LC/MS. Kinetic experiments were used to study hydrazone formation and exchange on resin yielding similar results to those obtained previously in solution. Competition experiments showed that the system reaches thermodynamic equilibrium if multiple hydrazides are added to the resin. Finally, competition experiments showed that the immobilized phosphonate-target indeed amplifies the capture of those hydrazides able to develop stabilizing interactions with the target. Importantly, the obtained amplification profile was nearly identical to the ones obtained previously in solution studies. Notably, the observed amplification factors for the self-selected hydrazides were higher, which was attributed to steric effects imposed by the resin.
    Organic & Biomolecular Chemistry 08/2013; 11(38). DOI:10.1039/c3ob41301b · 3.56 Impact Factor
  • Fabrizio Mancin · Leonard J. Prins · Paolo Scrimin
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    ABSTRACT: Clusters of gold atoms in the range 1–100 nm of diameter are unstable and tend to aggregate to form insoluble materials but become very stable once passivated with a monolayer of organic molecules typically anchored on the surface via an Au–S bond. The properties of this monolayer as a reaction loci constitute the topic of this overview of the recent literature. In analyzing the examples reported with functionalized monolayers we show how efficient catalysts these systems may become. Several data point out the occurrence of unusual reaction pathways and significant cooperativity between functional groups not observed not only in monomeric equivalent catalysts but also in other aggregation colloids like micelle and vesicles. The picture that emerges is that of a unique environment mimicking several features of enzymatic processes.
    Current Opinion in Colloid & Interface Science 02/2013; 18(1):61–69. DOI:10.1016/j.cocis.2012.12.003 · 5.84 Impact Factor
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    ABSTRACT: The development of a serine protease model using a self-selection protocol is described. The developed system mimics the regeneration step of an enzyme involved in covalent enzyme catalysis. A transition-state analogue of a transesterification reaction is used to self-select functional groups able to accelerate ester cleavage. It is shown that the insertion of a tertiary amine substituent flanking the reaction center reinforces transition-state stabilization by directing the reactive center towards the self-selected functionality. In addition, the tertiary amine activates a bland (solvent) nucleophile for attack on an ester bond similar to what occurs in a serine protease. A quantitative correspondence is observed between the amplification factors and catalytic activity, illustrating the potential of the dynamic covalent capture strategy to precisely detect and quantify weak noncovalent interactions.
    Israel Journal of Chemistry (Online) 02/2013; 53(1‐2). DOI:10.1002/ijch.201200080 · 2.22 Impact Factor
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    Davide Zaramella · Paolo Scrimin · Leonard J Prins
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    ABSTRACT: Histidine-containing peptides self-assemble on the surface of monolayer protected gold nanoparticles to form a catalytic system for transesterification reactions. Self-assembly is a prerequisite for catalysis, since the isolated peptides do not display catalytic activity by themselves. A series of catalytic peptides and substrates are studied in order to understand the structural parameters that are of relevance to the catalytic efficiency of the system. It is shown that the distance between the His-residue and the anionic tail does not affect the catalytic activity. On the other hand, the catalytic His-residue is sensitive to the chemical nature of the flanking amino acid residues. In particular, the presence of polar Ser-residues causes a significant increase in activity. Finally, kinetic studies of a series of substrates reveal that substrates with a hydrophobic component are very suitable for this catalytic system.
    International Journal of Molecular Sciences 01/2013; 14(1):2011-21. DOI:10.3390/ijms14012011 · 2.86 Impact Factor
  • Grégory Pieters · Cristian Pezzato · Leonard J Prins
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    ABSTRACT: A combination of hydrophobic and electrostatic interactions drives the self-assembly of a large number of small molecules on the surface of a monolayer protected gold nanoparticle. The hydrophobic interactions originate from the insertion of an aromatic unit in the hydrophobic part of the monolayer. This is evidenced by a shift in the emission wavelength of the fluorogenic probe upon binding. Up to around 35 small molecules can be simultaneously bound to the monolayer surface at micromolar concentrations in water. It is shown that an understanding of the supramolecular interactions that drive complex formation on the monolayer surface provides an unprecedented control over the supramolecular chemistry occuring on the surface. Taking advantage of the different kind of noncovalent interactions present in different probes it is possibile to selectively displace one type of surface bound molecules from a heteromeric surface. Finally, it is also possible to selectively 'catch-and-release' one type of surface bound molecules.
    Langmuir 12/2012; 29(24). DOI:10.1021/la304316z · 4.46 Impact Factor
  • Cristian Pezzato · Boram Lee · Kay Severin · Leonard J Prins
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    ABSTRACT: A sensing system has been obtained by self-assembly of multiple fluorescent indicators and monolayer protected gold nanoparticles. The system is able to discriminate between each of the eight nucleotides NDP and NTP (N = A, T, G, C) in a quantitative manner at micromolar concentrations.
    Chemical Communications 11/2012; 49(5). DOI:10.1039/c2cc38058g · 6.83 Impact Factor
  • Giulio Gasparini · Marta Dal Molin · Andrea Lovato · Leonard J. Prins
    ChemInform 09/2012; 43(37). DOI:10.1002/chin.201237259
  • Grégory Pieters · Cristian Pezzato · Leonard J Prins
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    ABSTRACT: The reversible "catch-and-release" of small molecules from the surface of monolayer-protected gold nanoparticles is described. The valency of the system (i.e., the number of molecules bound to the surface) can be controlled through the addition and removal of metal ions from the monolayer. Both the change in valency and the release rate of the molecules are strongly pH-dependent. The release rate can be regulated by altering the ratio of metal ions in the monolayer.
    Journal of the American Chemical Society 09/2012; 134(37):15289-92. DOI:10.1021/ja307621d · 12.11 Impact Factor
  • Grégory Pieters · Leonard J. Prins
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    ABSTRACT: This review describes the attractiveness of catalytic self-assembled monolayers (SAMs) on gold nanoparticles as catalytic systems. The hybrid inorganic–organic catalytic systems combine the advantages of homogeneous and heterogeneous catalysis (higher activity and catalyst recycling, respectively). The high fidelity process of SAM formation on gold nanoparticles, together with the possibility of making mixed SAMs composed of different thiols, provides an unprecedented route to stable, complex catalytic systems. Insertion of catalysts in a mixed monolayer can improve the catalytic performances, due to catalyst orientation, changes in the local chemical environment, or through the steering effect of neighbouring thiols. Alternatively, insertion of catalytic units in a monolayer may be an essential prerequisite in the case when catalysis requires cooperation between two catalytic units (for instance two metal ions). Finally, the multivalent nature of these systems is an important feature especially in the case when the substrate contains multiple reactive sites. Catalytic SAMs on gold nanoparticles also find applications beyond the field of catalysis, for instance in diagnostics and nanotechnology.
    New Journal of Chemistry 08/2012; 36(10-DOI: 10.1039/C2NJ40424A). DOI:10.1039/C2NJ40424A · 3.09 Impact Factor
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    ABSTRACT: The peptide sequence AcNH–TEG–Glu-Aib-Trp-AibAib-Trp-AibAib-Ile-Asp–OH (1), designed to display the WWI epitope found near the C-terminus of gp41, an envelope glycoprotein decorating the surface of the HIV-1 virus, has been synthesized and proved to have a relevant content of helical conformation because of the presence of five α-aminoisobutyric acid (Aib) units. Three copies of it have been connected to a tripodal platform based on 2,4,6-triethylbenzene-1,3,5-trimethylamine. The tripodal template 2 is even more structured than 1 thus suggesting a significant interaction between the three sequences connected to the platform. Preliminary inhibition assays of HIV-mediated cell fusion indicated that while the single peptide 1 is inactive within the concentration range of our assay, when it is conjugated to the tripodal platform, it is moderately active. These promising results suggest that our approach constitute a valid alternative to those reported so far.
    Tetrahedron 06/2012; 68(23):4346–4352. DOI:10.1016/j.tet.2012.03.078 · 2.64 Impact Factor