Nucleopeptides for biomedical strategies

Project leaders

Giovanni Roviello, Marina Pirtskhalava

Agreement

GEORGIA - SRNSF - Shota Rustaveli National Science Foundation

Call

CNR/SRNSF 2014-2015

Department

Biomedical sciences

Thematic area

Biomedical sciences

Status of the project

Extended

Report for renewal

finalreportroviellopirtskhalava.pdf

Research proposal

As a prosecution of the previuos research efforts of our joint research project of past two years, we aim to continue our study on peptides derivatized with DNA nucleobases, also referred as nucleopeptides (Roviello GN, et al. Amino Acids. 2010, 39:45-57). Our interest in nucleopeptides is justified on the basis of their interesting binding properties towards biomolecules (for example proteins or nucleic acids) of medical importance. In particular, the antiviral activity of nucleobase-carrying peptides, able to inhibit some viral retrotranscriptases (Roviello GN et al. J Med Chem. 2011, 54:2095-2101; Roviello GN et al. Amino Acids. 2010, 39:795-800), is an important feature in the field of the developement of novel anti-HIV drugs which was studied in this research project. Furthermore, the ability of these hybrid molecules to strongly bind poly rA tracts (Roviello GN et al. Amino Acids. 2010, 39:795-800 and Roviello GN et al. Amino Acids. 2012, 43:2537-2543) is another interesting point which was carefully investigated, since poly rA was recently recognized as a fundamental target in anticancer strategy due to the high level of polyadenylation of RNA in cancer cells (Topalian SL et al. Mol Cell Biol. 2001,21:5614-23). It was found that the nucleopeptide realized during 2012-2013 period was able to interact with poly rA and HIV RT, which are both characteristics of biomedical importance. Computational studies performed by Pirtskhalava's team threw light on the nature of the molecular recognition based on the nucleopeptide. Since it is necessary to plan the possible structural modifications useful to improve the binding properties of this potential antitumor and antiviral drug, a extensive study on the chemistry of the interaction, accompanied by a deep investigation of the structural features of the binding (based on on both experimental and computer-assisted theoretical studies), is clearly desirable and is object of the present research proposal.

Research goals

1-to study the stoichiometry of the complexes formed by the nucleopeptide with the biomolecules under investigation;

2-to give information on the moleculare features influencing the formation of the complexess;

3-to perform computational studies in support of the experimental/spectroscopic data leading to the design to improved poly rA-binders and HIV RT inhibitors.

Last update: 07/08/2025