Nucleic acid chemistry
Ramon Eritja
Principal Investigator
Professor (IBMB-CSIC)
Office Tel : +34 93 400 61 45 // +34 93 403 99 41
Lab Tel : +34 93 403 99 42
e-mail : ramon.eritja
irbbarcelona.org
Background
Nucleic acids (DNA and RNA), which are formed by long chains of nucleotides, play a crucial role in genetic inheritance. Oligonucleotides (small versions of nucleic acids) have been synthesized in laboratories since the 1980s. The field of nucleic acid chemistry has since undergone remarkable progress, which has been vital for the development of several disciplines such as biochemistry, molecular biology, structural biology, biotechnology, biomedicine and, in more recent years, nanoscience.
Research Interests
To synthesize oligonucleotides and nucleic acid derivatives in order to study their properties, and also to further develop and improve techniques involving oligonucleotides.
Research Lines
Two major research lines are underway:
1) Synthesis of modified oligonucleotides to be used in the fabrication of molecular circuits based on DNA.
Since the fabrication of the first chips in the 1950s, the density of the functional units per surface unit has duplicated every 3-4 years. This advance has been achieved thanks to technological breakthroughs that have allowed circuit miniaturization. However, currently available technologies based on photolithography are reaching their physical limits. Thus, it is believed that in the near future parts of the circuits will be prepared using biomolecules, which will arrange the nanomaterials in solution while the resulting structures will be positioned in the spaces produced by photolithography. One of the promising biomolecules for this approach is DNA. In this regard, we have developed a methodology to synthesize modified oligonucleotides, which are then used to assemble nanomaterials. The most important result from this research is the selective metallization, with gold nanoparticles, of a linear DNA structure formed by synthetic oligonucleotides (Ongaro, et al. (2004) Adv. Mat., 16, 1799). We are now increasing the complexity of the system by preparing new oligonucleotide derivatives. For the functionalization of nanomaterial surfaces, we are also preparing oligonucleotides by means of molecules that have electronic properties of interest and also through the use of reactive groups.
2) Synthesis of oligonucleotides carrying 8-aminopurines and study of the stabilization properties of triple helices.
The capacity of several synthetic oligonucleotides to inhibit gene expression has generated great interest in the scientific community. This capacity makes these molecules potential therapeutic drugs for the treatment of viral infections and cancer (antisense therapy). On the basis of using triple formation, we are currently working on the development of new oligonucleotide derivatives that inhibit gene expression. We have demonstrated that the presence of 8-aminopurines stabilize triple helices. We aim to use these stabilizing properties to obtain oligonucleotides with more potent inhibitory activity. To date we have demonstrated that hairpin affinity is so high that the oligonucleotides can bind target sequences with secondary structures, thereby competing successfully with these and yielding the expected triplex.
Funding
This group receives financial support from the following sources:
- Fundació "la Caixa" ("la Caixa" Foundation)
- European Commission
- Generalitat de Catalunya (Government of Catalonia)
- Ministerio de Educación y Ciencia (Spanish Ministry of Science and Education)
More info
Nucleic acid chemistry
8-Amino guanine accelerates tetramolecular G-quadruplex formation
Gros J, Aviñó A, Lopez de la Osa J, González C, Lacroix L, Pérez A, Orozco M, Eritja R and Mergny JL
Chem Commun, 7 (25), 2926-2928 (2008)
Synthesis of oligonucleotide derivatives using ChemMatrix supports
Mazzini S, García-Martin F, Alvira M, Aviñó A, Manning B, Albericio F and Eritja R
Chem Biodivers, 5 (1), 209-218 (2008)
Incorporation of zebularine from its 2'-deoxyribonucleoside triphosphate derivative and activity as a template-coding nucleobase
Dowd CL, Sutch BT, Haworth IS, Eritja R, Marquez VE and Yang AS
Nucleosides Nucleotides Nucleic Acids, 27 (2), 131-145 (2008)
Protecting groups for RNA synthesis: an increasing need for selective preparative methods
Somoza A
Chem Soc Rev, 37 (12), 2675-2688 (2008)
Study of the interaction between the G-quadruplex-forming thrombin-binding aptamer and the porphyrin 5,10,15,20-tetrakis-(N-methyl-4-pyridyl)-21,23H-porphyrin tetratosylate
Del Toro M, Gargallo R, Eritja R and Jaumot J
Anal Biochem, 379 (1), 8-15 (2008)
Solid-phase synthesis of oligomers carrying several chromophore units linked by phosphodiester backbones
Aviñó A, Navarro I, Farrera-Sinfreu J, Royo M, Aymamí J, Delgado A, Llebaria A, Albericio F and Eritja R
Bioorg Med Chem Lett, 18 (7), 2306-2310 (2008)
Design, synthesis and antiproliferative properties of oligomers with chromophore units linked by amide backbones
Farrera-Sinfreu J, Aviñó A, Navarro I, Aymamí J, Beteta NG, Varón S, Pérez-Tomás R, Castillo-Avila W, Eritja R, Albericio F and Royo M
Bioorg Med Chem Lett, 18 (7), 2440-2444 (2008)
Synthesis of oligonucleotide conjugates carrying viologen and fluorescent compounds
Alvira M, Quinn SJ, Aviñó A, Fitzmaurice D and Eritja R
The Open Org Chem J, 2, 41-45 (2008)
Experimental measurement of carbohydrate aromatic stacking in water using a dangling-ended DNA model system
*Comments on News and Views Nat Chem Biolhttp://www.nature.com/nchembio/journal/v4/n10/full/nchembio1008-586.html Morales JC, Reina JJ, Díaz I, Aviñó A, Nieto PM and Eritja R
Chemistry, 14 (26), 7828-7835 (2008)
Solid-phase synthesis of modified oligonucleotides
Eritja R
Int J Pept Res Ther, 13 (1-2), 53-68 (2007)
Analysis of interaction between dendriplexes and bovine serum albumin
Shcharbin D, Pedziwiatr E, Chonco L, Bermejo-Martín JF, Ortega P, de la Mata FJ, Eritja R, Gómez R, Klajnert B, Bryszewska M and Muñoz-Fernandez MA
Biomacromolecules, 8 (7), 2059-2062 (2007)
ds-Oligonucleotide-peptide conjugates featuring peptides from the leucine-zipper region of Fos as switchable receptors for the oncoprotein Jun
Portela C, Albericio F, Eritja R, Castedo L and Mascareñas JL
ChemBiochem, 8 (10), 1110-1114 (2007)
Solution equilibria of the i-motif-forming region upstream of the B-cell lymphoma-2 P1 promoter
Khan N, Aviñó A, Tauler R, González C, Eritja R and Gargallo R
Biochemie, 89 (12), 1562-1572 (2007)
Triplex formation using oligonucleotide clamps carrying 8-aminopurines
Aviñó A, Grimau MG, Alvira M, Eritja R, Gargallo R, Orozco M and González C
Nucleosides Nucleotides Nucleic Acids, 26 (8-9), 979-983 (2007)
New developments on the synthesis of oligonucleotide-peptide conjugates
Portela C, Mascareñas JL, Albericio F, Mazzini S, Caminal C, Ramos R, Ocampo SM and Eritja R
Nucleosides Nucleotides Nucleic Acids, 26 (8-9), 963-967 (2007)
A flexible method for the fabrication of gold nanostructures using oligonucleotide derivatives
Eritja R, Aviñó A, de la Torre BG, Fitzmaurice D, Ongaro A, Stanca SE, DiSalvo A, Maninng B and Iacopino D
Nucleosides Nucleotides Nucleic Acids, 26 (10-12), 1605-1609 (2007)
Water-soluble carbosilane dendrimers protect phosphorothioate oligonucleotides from binding to serum proteins
Chonco L, Bermejo-Martín JF, Ortega P, Shcharbin D, Pedziwiatr E, Klajnert B, de la Mata FJ, Eritja R, Gómez R, Bryszewska M and Muñoz-Fernandez MA
Org Biomol Chem, 5 (12), 1886-1893 (2007)
Water-soluble carbosilane dendrimers: synthesis biocompatibility and complexation with oligonucleotides; evaluation for medical applications
Bermejo JF, Ortega P, Chonco L, Eritja R, Samaniego R, Müllner M, de Jesus E, de la Mata FJ, Flores JC, Gomez R and Muñoz-Fernandez A
Chemistry, 13 (2), 483-495 (2007)
Spectroscopic study of the interaction of actinomycin D with oligonucleotides carrying the central base sequences -XGCY- and -XGGCCY- using multivariate methods
Vives M, Tauler R, Eritja R and Gargallo R
Anal Bioanal Chem, 387 (1), 311-320 (2007)
Synthesis of oligonucleotides carrying 5’-5’ linkages using copper-catalyzed cycloaddition reactions
Alvira M and Eritja R
Chem Biodivers, 4 (12), 2798-2809 (2007)
Traightforward access to simplified sphingosine-1-phosphate analogues
Grijalvo S, Llebaria A and Delgado A
Synthetic Comm, 37, 2737-2751 (2007)
Solid-phase synthesis of a combinatorial library of dehydroceramide analogues and its activity in human alveolar epithelial cells
Villorbina G, Canals D, Carde L, Grijalvo S, Pascual R, Rabal O, Teixidó J, Fabriàs G, Llebaria A, Casas J and Delgado A
Bioorg Med Chem, 15 (1), 50-62 (2007)
A simple DNA-based traslation system
Garibotti AV, Liao S and Seeman NC
Nano Lett, 7 (2), 480-483 (2007)
Efficient sequence-specific purification of Listeria innocua mRNA species by triplex affinity capture with parallel tail-clamps
Nadal A, Coll A, Aviñó A, Esteve T, Eritja R and Pla M
Chembiochem, 7 (7), 1039-1047 (2006)
Destabilization of quadruplex DNA by 8-aminoguanine
López de la Osa J, González C, Gargallo R, Rueda M, Cubero E, Orozco M, Aviñó A and Eritja R
Chembiochem, 7 (1), 46-48 (2006)
Resolution of a structural competition involving dimeric G-quadruplex and its C-rich complementary strand
Jaumot J, Eritja R, Tauler R and Gargallo R
Nucleic Acids Res, 34 (1), 206-216 (2006)
Trimethylguanosine nucleoside inhibits cross-linking between Snurportin 1 and m3G-CAPPED U1 snRNA
Bahia D, Aviñó A, Darzynkiewicz E, Eritja R and Bach-Elias M
Nucleosides Nucleotides Nucleic Acids, 25 (8), 909-923 (2006)
Comparative uptake of phosphorothioate oligonucleotides by human peripheral blood mononuclear cells from newborns and adults
Bermejo JF, Chonco L, Samaniego R, Fernández G, Eritja R and Muñoz-Fernández MA
Eur J Sci Res, 15, 113-121 (2006)
DNA-templated assembly of nanoscale architectures for next-generation electronic devices
Stanca SE, Eritja R and Fitzmaurice D
Faraday Discuss, 131, 155-165 (2006)
DNA-templated assembly of nanoscale architectures
Stanca SE, Eritja R and Fitzmaurice D
Nanotechnology, 16 (9), 1905-1911 (2005)
A straightforward synthesis of 5'-peptide oligonucleotide conjugates using N(alpha)-Fmoc-protected amino acids
Ocampo SM, Albericio F, Fernández I, Vilaseca M and Eritja R
Org Lett, 7 (20), 4349-4352 (2005)
Magnetically trigged direct electrochemical detection of DNA hybridization using Au67 quantum dot as electrical tracer
Pumera M, Castañeda MT, Pividori MI, Eritja R, Merkoçi A and Alegret S
Langmuir, 21 (21), 9625-9629 (2005)
Toward an ICPMS-linked DNA assay based on gold nanoparticles immunoconnected through peptide sequences
Merkoçi A, Aldavert M, Tarrasón G, Eritja R and Alegret S
Anal Chem, 77 (19), 6500-6503 (2005)
"Parallel" and "antiparallel tail-clamps" increase the efficiency of triplex formation with structured DNA and RNA targets
Nadal A, Eritja R, Esteve T and Pla M
Chembiochem, 6 (6), 1034-1042 (2005)
Synthesis and triplex-forming properties of cyclic oligonucleotides with (G,A)-antiparallel strands
Grimau MG, Gargallo R, Aviñó A and Eritja R
Chem Biodivers, 2 (2), 275-285 (2005)
Strand displacement of double-stranded DNA by triples-forming antiparallel purine-hairpins
Coma S, Noé V, Eritja R and Ciudad CJ
Oligonucleotides, 15 (4), 269-283 (2005)
Synthesis of oligonucleotide-peptide conjugates carrying the c-myc peptide epitope as recognition system
Frieden M, Aviñó A, Tarrasón G, Escorihuela M, Piulats J and Eritja R
Chem Biodivers, 1 (6), 930-938 (2004)
Synthesis, stability, and protonation studies of a self-complementary dodecamer containing the modified nucleoside 2'-deoxyzebularine
Vives M, Eritja R, Tauler R, Marquez VE and Gargallo R
Biopolymers, 73 (1), 27-43 (2004)
Monitoring denaturation behaviour and comparative stability of DNA triple helices using oligonucleotide-gold nanoparticle conjugates
Murphy D, Eritja R and Redmond G
Nucleic Acids Res, 32 (7), e65 (2004)
Hybridization and melting behaviour of peptide nucleic acid-oligonucleotide chimeras conjugated to gold nanoparticles
Murphy D, Redmond G, De la Torre BG and Eritja R
Helv Chim Acta, 87, 2727-2734 (2004)
DNA templated assembly of a protein-functionalized nanogap electrode
Ongaro A, Griffin F, Nagle L, Iacopino D, Eritja R and Fitzmaurice D
Adv Materials, 16, 1799-1803 (2004)
Synthesis and triple-helix stabilization properties of branched oligonucleotides carrying 8-aminoadenine moieties
Aviñó A, Grimau MG, Frieden M and Eritja R
Helv Chim Acta, 87, 303-316 (2004)
Resolution of parallel and antiparallel oligonucleotide triple helices formation and melting processes by multivariate curve resolution
Jaumot J, Eritja R, Aviñó A, Tauler R and Gargallo RJ
Biomol Struct Dyn, 21 (2), 267-278 (2003)
Potent inhibition of HhaI DNA methylase by the aglycon of 2-(1H)-pyrimidinone riboside (zebularine) at the GCGC recognition domain
Marquez VE, Eritja R, Kelley JA, Vanbemmel D and Christman JK
Ann N Y Acad Sci, 1002, 154-164 (2003)
Antiparallel triple helices. Structural characteristics and stabilization by 8-amino derivatives
Aviñó A, Cubero E, González C, Eritja R and Orozco M
J Am Chem Soc, 125 (51), 13127-16138 (2003)
Synthesis of branched oligonucleotides as templates for the assembly of nanomaterial
Grimau MG, Iacopino D, Aviñó A, De la Torre BG, Ongaro A, Fitzmaurice D, Wessels J and Eritja R
Helv Chim Acta, 86 (8), 2814-2826 (2003)
Peptide-PNA conjugates: targeted transport of antisense therapeutics into tumors
Mier W, Eritja R, Mohammed A, Haberkorn U and Eisenhut M
Angew Chem Int Ed Engl, 42 (17), 1968-1971 (2003)
Imaging the DNA and nanoparticle components of a self-assembled nanoscale architecture
Iacopino D, Ongaro A, Nagle L, Eritja R and Fitzmaurice D
Nanotechnology, 14 (4), 447-452 (2003)
DNA-controlled assembly of protein-modified gold nanocrystals
Cobbe S, Connolly S, Nagle L, Eritja R, Fitzmaurice D and Ryan D
J Phys Chem B, 107 (2), 470-477 (2003)
