Structure-function studies in synthetic models of nucleic acids

 

TITLE

Structure-function studies in synthetic models of nucleic acids

STAFF

Luciano Cellai*
Cecilia Bartolucci
Doriano Lamba
Andrea Margonelli
Giuseppina Andreano*
Annalisa Masi*
[*] not in permanent position

CNR MODULE

PM.P06.001.001 Cristallography of Biomolecules and Functional Studies

KEYWORDS

Models of nucleic acids, Structure-Function Relationships, Structural Biology

COLLABORATIONS
ISOF CNR (www.isof.cnr.it)
University of Rome La Sapienza (www.chem.uniroma1.it)
University of Siena (www.chim.unisi.it)
Max-Planck-Institut fuer Biochemie, Muenchen (www.biochem.mpg.de)
COST Action Chembioradical (www.cost.esf.org/Free_Radicals_in_Chemical_Biology)
DESCRIPTION

Models of nucleic acids (DNA, RNA, chimeric, base and backbone modified) can be prepared in large amounts according to standard automated synthetic methods. This technology was exploited by our group for collaborating to studies on the mechanism of replication of HIV-1 and mechanisms of resistance in HCV [1,2]. Studies were also performed aimed at the introduction of EPR and NMR sensitive probes into nucleic acid models [3, 4] and on the mechanism of action of aminoglycosidic antibiotics on rRNA [5]. More recently the activity has been extended to the study of the molecular basis of DNA damage by radical species and of the interaction of anticancer compounds with telomeric DNA, as a contribution to their anticancer activity.

[1] Szyperski T., Goette M., Billeter M., Perola E., Cellai L., Heumann H., Wuetrich K. "NMR Structure of the Chimeric Hybrid Duplex r(gcaguggc)-r(gcca)d(CTGC) Comprising the tRNA-DNA Junction Formed During Initiation of HIV-1 Reverse Transcription". J. Biomol. NMR, 13, 343-355, 1999
[2] Deval J., Powdrill M.H., D'Abramo C., Cellai L., Goette M."Pyrophosphorolytic excision of non-obligate chain-terminators by Hepatitis C virus NS5B polymerase". Antimicrob. Agents Chemother. 51, :2920-8, 2007
[3] Giordano C., Fratini F., Attanasio D., Cellai L."Preparation of Spin-Labeled 2-Amino-dA, dA, dC and 5-Methyl-dC Phosphoramidites for the Automatic Synthesis of EPR Active Oligonucleotides".Synthesis, 4, 565-572, 2001.
[4] Chirivino E., Giordano C., Faini S., Cellai L., Fragai M. "Tuning Sensitivity in Paramagnetic NMR Detection of Ligand-DNA Interactions". ChemMedChem. 2, 1153-6, 2007
[5] Structural features of apramycin bound at the bacterial ribosome A-site as detected by NMR and CD spectroscopy. Balenci D, D'Amelio N, Gaggelli E, Gaggelli N, Cellai L, Molteni E, Valensin G. Chembiochem. 2010 Jan 25;11(2):166-9.

 

Structure-function studies in synthetic models of nucleic acids - Img

1H NMR study of the effect of Cu(II) on the complex between Kanamycin A and an RNA fragment that mimics the bacterial ribosomal A Site.

 

Structure-function studies in synthetic models of nucleic acids - Img

Geometrical parameters of two possible copper sites in the kanamycin-RNA complex. Guanine, adenine, and cytosine bases are represented in green, red, and violet, respectively. Copper is represented as a yellow sphere (D. Balenci et al. ChemBioChem 2008, 9, 114-123)

CONTACTS

 

Dr. Luciano Cellai
Email : luciano.cellaiATic.cnr.it
Tel : +39 0690 672 613

 

Last Updated (Monday, 25 October 2010 13:53)