MOM – Mimicking Organic Metabolites

Prof. Daniela Montesarchio

Room 1Mb14; phone +39-081-674126/41 Email daniela.montesarchio@unina.it;

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Prof. Daniela Musumeci

Room 1Mb17; phone +39-081-674143/41 Email domenica.musumeci@unina.it;

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Prof. Vincenzo Piccialli

Room 0Mb10; phone +39-081-674111 Email vincenzo.piccialli@unina.it;

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Other Group members:

post-Doc: dr. Claudia Ricciardi, dr. Chiara Platella;

PhD Students: dr. Ettore Napolitano

 

Research: Our research is focused on the design, synthesis and applications of bioactive compounds, mainly oligonucleotides, but also peptidomimetics, glycomimetics and small molecules, including nucleosides, nucleotides and their analogues, aiming at: (i) elucidation of their main structural features; (ii) insight into their structure-activity relationships and their interactions; (iii) discovery of new molecules specifically inhibiting/modulating biomedically relevant targets in vivo as effective drugs; (iv) development of biosensors. Main research topics of our group are:

 

Oligonucleotide-based aptamers as anticancer, anti-inflammatory, antiviral and anticoagulant drugs. Aptamers are single-stranded DNA or RNA oligonucleotides able to recognize with high affinity and selectivity specific targets due to their peculiar three-dimensional folding. Generally identified from large combinatorial libraries of random oligonucleotide sequences via an iterative procedure known as SELEX (Systematic Evolution of Ligands by EXponential enrichment), aptamers are then optimized via different, mainly rationally guided approaches. In our group, we investigate novel aptamers active as anticancer, anti-inflammatory, antiviral or anticoagulant agents, evaluating their conformational features, their interactions with the respective targets and their bioactivity, in order to identify the best aptamers for specific therapeutic and diagnostic applications.

Main collaborations:

  • Proff. Francois Morvan and Jean-Jacques Vasseur (Universitè de Montpellier 2, Montpellier);

  • Prof. Prabodhika Mallikaratchy (Department of Chemistry, CUNY, New York).

  • Proff. Angela Arciello, Luigi Petraccone, Irene Russo-Krauss and Luigi Paduano (Department of Chemical Sciences, Federico II University of Naples).

 

G-quadruplex (G4) structures of DNA. G-quadruplexes are non-canonical structures of DNA and RNA formed via stacking of two or more G-quartets, i.e. cyclic planar arrangements of four guanines held together via Hoogsteen H-bonds, also stabilized by monovalent cations as K+ or Na+. In vivo, G-quadruplex structures are spontaneously formed near the ends of chromosomes, known as telomeres, and in transcriptional regulatory regions of multiple genes, including oncogenes in humans. In this field, we investigate the structure/function relationships of G-quadruplex forming oligonucleotides and search for selective G4-targeting ligands, i.e. small molecules able to specifically bind and stabilize G-quadruplex structures in telomeres or oncogenes, thus inhibiting their cancer-related activities in targeted antitumoral therapies.

Main collaborations:

  • Prof. Janez Plavec (Slovenian NMR Centre, Ljubljana);
  • Proff. Luigi Petraccone (Department of Chemical Sciences, Federico II University of Naples);
  • Proff. Concetta Giancola, Antonio Randazzo, Jussara Amato and Bruno Pagano (Department of Pharmacy, Federico II University of Naples);
  • Proff. Mauro Freccero and Filippo Doria (Department of Chemistry, University of Pavia);
  • Dr. Annamaria Biroccio (Regina Elena Tumour Institute, Rome).

 

Metal-based anticancer drugs: Ru(III) and Pt(II) complexes. The great advances in the studies on metal complexes for the treatment of different cancer forms, starting from the pioneering works on Pt derivatives, have fostered an increasingly growing interest in their properties and biomedical applications. Our research is focused on the design, synthesis, characterization and analysis of Pt(II) and Ru(III)-complexes incorporating various ligands, such as (nucleo)aminoacids and nucleolipids, as well as on the elucidation of their DNA-binding properties and antiproliferative activity.

Main collaborations:

  • Proff. Luigi Paduano, Gerardino D'Errico, Antonello Merlino and Marco Trifuoggi (Department of Chemical Sciences, Federico II University of Naples);
  • Proff. Carlo Irace, Rita Santamaria, Francesco Maione and Domenica Capasso (Department of Pharmacy, Federico II University of Naples);
  • Dr. Giovanni N. Roviello and Sonia Di Gaetano (IBB-CNR, Napoli);
  • Prof. Luigi Messori (Department of Chemistry "Ugo Shiff", University of Florence);
  • Prof. Wolfgang Weigand (Institute of Inorganic Chemistry Chemistry, University of Jena).

 

Synthesis and characterization of multifunctionalized nanoparticles for theranostic applications. Nanoparticles are valuable drug delivery systems, offering wide surfaces which can be easily functionalized with multiple copies of bioactive molecules, thus allowing enhanced activities by multivalency effects. In this field we investigate several nanosystems, including superparamagnetic iron oxide-based nanoparticles, of interest for diagnostic applications, silica-based nanoparticles, niosomes, etc., decorated with bioactive compounds of different nature – i.e., amphiphilic Ru(III) complexes, antinucleolin or antithrombin aptamers – for their anticancer or anticoagulant properties.

Main collaborations:

  • Prof. Ramon Eritja (IQAC, CSIC, Barcelona);
  • Prof. Luigi Paduano and Gerardino D'Errico (Department of Chemical Sciences, Federico II University of Naples).

 

Nucleopeptides as potential antivirals (DNA/RNA targets) and nanomaterials. Our efforts in this field are devoted to the design, synthesis and characterization of novel nucleopeptides and study of their hybridization properties (i) with complementary nucleic acid targets in therapeutic/diagnostic applications or (ii) with other nucleopeptides as innovative nanomaterials.

Main collaborations:

  • Dr. Giovanni N. Roviello (IBB-CNR, Napoli);
  • Prof. Andriy Mokhir (Friedrich Alexander University, Erlangen-Nürnberg, Germany);
  • Dr. Domenica Capasso (Department of Pharmacy, Federico II University of Naples).

 

Amphiphilic glycomimetics as synthetic ionophores. Amphiphilic molecules can spontaneously self-assemble in aq. solutions into a variety of supramolecular structures with peculiar properties. In this field we investigate amphiphilic nucleoside derivatives and cyclic oligosaccharides able to selectively transport cations through lipid membranes, showing antibiotic and anticancer activity.

Main collaborations:

  • Prof. Paolo Tecilla (Department of Chemical and Pharmaceutical Sciences, University di Trieste);
  • Proff. Carlo Irace and Rita Santamaria (Department of Pharmacy, Federico II University of Naples);
  • Prof. Gerardino D'Errico and Luigi Paduano (Department of Chemical Sciences, Federico II University of Naples).

 

Searching for new biologically active compounds through synthesis, semi-synthesis and isolation from natural sources. Natural products have historically served as leads for drug development as nature offers a myriad of molecular architectures selected over millions of years of evolution. Our group is involved in the synthesis of analogues, or the isolation from natural sources, of biologically active substances belonging to different chemical classes such as polyoxygenated steroids, halogenated C15 acetogenins and mixed polyketide-peptide compounds of marine origin.

Main collaborations:

  • Proff. Nicola Borbone, Monica Terracciano, Valeria Costantino, Domenica Capasso (Department of Pharmacy, University of Naples Federico II);
  • Prof. Agostino Casapullo (Department of Pharmacy, University of Salerno);
  • Dr. Sonia di Gaetano (Institute of Biostructure and Bioimaging, CNR, Naples).