1,721,179 research outputs found
Synthesis, characterization and biological activities of DNA G-quadruplexes
No full textDr. Nicola Borbone presented the research activities focalized on DNA quadruplexes run in the laboratories of the School of Pharmacy of the University of Napoli “Federico II”.
During his talk Dr. Borbone discussed the following topics:
1. Instrumentation available at the School of Pharmacy in Napoli.
2. Synthesis of DNA putative quadruplex sequences containing modified residues.
3. Synthesis of Tetra-End-Linked (TEL) monomolecular quadruplexes.
4. Synthesis of PNAs capable to bind to DNA quadruplexes as quadruplex ligands.
5. Construction of TEL-ODN based nanodevices to be used as novel biosensors.
6. Synthesis of TEL-aptamers and short PNAs to be used as novel anticancer drugs
New anti-HIV aptamers with enhanced activity based on tetra-end-linked G-quadruplex-forming oligonucleotides
No full textThe first stage of the HIV infection requires the entry of human immunodeficiency virus (HIV) into host cells. This stage involves the sequential interaction of the virion surface glycoprotein gp120 with the CD4 glycoprotein and a chemokine receptor on the host cell surface.1 The CD4 glycoprotein is expressed on the surface of T-lymphocytes, monocytes, dendritic cells and brain microglia, and its expression makes these cells a target for HIV in vivo. The third variable region of gp120 – known as V3-loop – is a pivotal component of the co-receptor binding site, thus making it a target for pharmaceutical intervention.
The first anti-HIV aptamers targeted against the V3 loop appeared in the literature in 2004, when H. Hotoda (SA-1042)2 and J. R. Wyatt (ISIS 5320)3 indipendently showed that chemically-modified selected G-quadruplex-forming ODN aptamers are capable to bind the V3 loop of gp120, thus protecting host cells from HIV infection. In the following years several analogs of SA-1042 have been proposed with the aim to improve both the anti-HIV activity and resistance to nucleases. This communication reports on the synthesis and biophysical, biological and SAR studies of a small library of new analogs of SA-1042 based on G-quadruplex-forming Tetra-End-Linked (TEL) oligonucleotides.4 The new aptamers showed EC50 values against HIV-1 in the range of 0.04-0.15 μM, as well as affinities for the HIV-1 gp120 envelope at the same order of magnitude
New HIV-1 aptamers with enhanced activity based on tetra-end-linked G-quadruplex-forming oligonucleotides
No full textAnti HIV activity of monomolecular tetra-end-linked analogues of the SA-1042 aptamer targeted against the viral envelope glycoprotein gp120
No full textThe first stage of the HIV infection requires the entry of HIV virus into host cells. This stage involves the sequential interaction of the viral envelope glycoprotein gp120 with the CD4 glycoprotein and chemokine receptors on the host cell surface. The third hyper variable region of gp120 (V3 loop) has been identified as the pivotal component of the co-receptor binding site. The V3 loop typically consists of a 35 aminoacids loop closed by two cysteines forming a disulphide bridge. As emerged from the crystal structure of gp120 complexed with the CD4 receptor and a neutralizing antibody, the V3 loop protrudes from the protein core and is involved in the binding with the co-receptor. Given the important role played by the V3 loop for HIV-1 infection and pathogenesis many efforts are being devoted to the development of drugs targeted against it. Among the most promising alternatives is the use of aptamer technology. The first anti-HIV aptamers targeted against the V3 loop appeared in the literature in 1994 when H. Hotoda (SA-1042) and J.R. Wyatt (ISIS 5320) independently showed the ability of nucleases-resistant quadruplex-forming DNA aptamers to bind the V3 loop of gp120 thus protecting CD4+ cells from HIV infection. In 2010, considering that all the gp120-binding aptamers present in the literature needed chemical modifications to improve their resistance against nucleases and to improve the kinetics of quadruplex formation, we began a study aimed at the synthesis of a series of new monomolecular analogues of SA-1042 by exploiting the Tetra-End-Linker (TEL) strategy proposed by us in 2004. In the last four years several TEL-aptamers differing for the TEL size, the polarity of the ODN strands and lipophilic ending groups or for the ODN sequence and length have been synthesized in our laboratories. The main results obtained by chemical, biophysical, biological and SAR investigation are reported in this communication. The EC50 of new TEL-aptamers is as low as 0.039 μM
Sviluppo di una metodica per lo studio della sopravvivenza di consorzi microbici d'interesse agroalimentare.
No full textNew anti-HIV aptamers based on tetra-end-linked DNA G-quadruplexes: effects of the base sequence and ODN length on anti-HIV activity
No full textRuthenium-catalyzed oxidative cyclization of 1,7-dienes. A novel diasteroselective synthesis of 2,7-disubstituted trans-oxepane diols
No full textThe ruthenium-catalyzed oxidation of some representative 1,7-dienes has been investigated. Tetrasubstituted 1,7-dienes are transformed into the corresponding trans-2,7-bis-hydroxyalkyl-oxepanes through an oxidative cyclization process. The process proceeds with an excellent stereoselectivity level
RuO4-catalyzed oxidative polycyclization of the Cs-symmetric isoprenoid polyene digeranyl. An unexpected stereochemical outcome.
No full textThe RuO4-catalyzed oxidative polycyclization of digeranyl, a Cs-symmetric tetraene possessing a repetitive 1,5-diene structural motif, has been studied. The required substrate has been synthesized by Ti(III)-mediated tail-to-tail homocoupling of geranyl bromide. The process afforded two hitherto unknown isomeric tris-tetrahydrofuran products possessing unexpected all-threo cis–trans–cis and cis–trans–trans relative configuration. The new stereochemical outcome is explained based on previously formulated chelation or steric control models on the basis of structural differences between digeranyl and previously studied isoprenoid polyenes farnesyl acetate, geranylgeranyl acetate and squalene
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