Abstract
In this work, we report a synthetic approach to a Fmoc-protected nucleoamino acid, based on l-diaminopropanoic acid, carrying the DNA nucleobase on the alpha-amino group by means of an amide bond, suitable for the solid-phase synthesis of novel nucleopeptides of potential interest in biomedicine. After ESI–MS and NMR characterization this building block was used for the assembly of a thymine-functionalized nucleopeptide, composed of nucleobase-containing l-diaminopropanoic acid moieties and underivatized l-lysine residues alternated in the backbone. Circular dichroism studies performed on the cationic nucleopeptide and adenine-containing DNA and RNA molecules suggested that the thymine-containing peptide is able to interact with both DNA and RNA. In particular, a significant conformational variation in the RNA structure was suggested by CD studies. Human serum stability assays were also conducted on the cationic nucleopeptide, which was found to be highly resistant to enzymatic degradation.
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Abramova TV, Vlassov VV, Zarytova VF, Ivanova EM, Kuligina EA, Ryte AS (1991) The effect of oligodeoxyribonucleotide terminal phosphate and ribose modification on the interactions of oligonucleotides with cells and intracellular stability. Nucleosides Nucleotides 10:639–640
Bell NM, Micklefield J (2009) Chemical modification of oligonucleotides for therapeutic, bioanalytical and other applications. ChemBioChem 10:2691–2703
Calabretta A, Tedeschi T, Di Cola G, Corradini R, Sforza S, Marchelli R (2009) Arginine-based PNA microarrays for APOE genotyping. Mol BioSyst 5:1323–1330
D’Alonzo D, Guaragna A, Palumbo G (2011) Exploring the role of chirality in nucleic acid recognition. Chem Biodivers 8:373–413
Dragulescu-Andrasi A, Rapireddy S, He G, Bhattacharya B, Hyldig-Nielsen JJ, Zon G, Ly DH (2006) Cell-permeable peptide nucleic acid designed to bind to the 5′-untranslated region of E-cadherin transcript induces potent and sequence-specific antisense effects. J Am Chem Soc 128:16104–16112
Katritzky AR, Narindoshvili T (2008) Chiral peptide nucleic acid monomers (PNAM) with modified backbones. Org Biomol Chem 6:3171–3176
Krzyzanowska D, Lisowski M, Kochman M (1998) UV-difference and CD spectroscopy studies on juvenile hormone binding to its carrier protein. J Pept Res 51:96–102
Petraccone L, Pagano B, Esposito V, Randazzo A, Piccialli G, Barone G, Mattia CA, Giancola C (2005) Thermodynamics and kinetics of PNA-DNA quadruplex-forming chimeras. J Am Chem Soc 127:16215–16223
Rocchi R, Borin G, Marchiori F, Moroder L, Peggion E, Scoffone E, Crescenzi V, Quadrifoglio F (1972) Interaction of S-protein with S-peptide and with synthetic S-peptide analogs. A spectroscopic and calorimetric investigation. Biochemistry 11:50–57
Roviello GN, Moccia M, Sapio R, Valente M, Bucci EM, Castiglione M, Pedone C, Perretta G, Benedetti E, Musumeci D (2006) Synthesis, characterization and hybridization studies of new nucleo-gamma-peptides based on diaminobutyric acid. J Pept Sci 12:829–835
Roviello GN, Musumeci D, Moccia M, Castiglione M, Sapio R, Valente M, Bucci EM, Perretta G, Pedone C (2007) dabPNA: design, synthesis, and DNA binding studies. Nucleosides, Nucleotides Nucleic Acids 26:1307–1310
Roviello GN, Musumeci D, De Cristofaro A, Capasso D, Di Gaetano S, Bucci EM, Pedone C (2010a) Alternate dab-aegPNAs: synthesis, nucleic acid binding studies and biological activity. Mol BioSyst 6:199–205
Roviello GN, Benedetti E, Pedone C, Bucci EM (2010b) Nucleobase-containing peptides: an overview of their characteristic features and applications. Amino Acids 39:45–57
Roviello GN, Musumeci D, Pedone C, Bucci EM (2010c) Synthesis, characterization and hybridization studies of an alternate nucleo epsilon/gamma-peptide: complexes formation with natural nucleic acids. Amino Acids 38:103–111
Sforza S, Galaverna G, Dossena A, Corradini R, Marchelli R (2002) Role of chirality and optical purity in nucleic acid recognition by PNA and PNA analogs. Chirality 14:591–598
van der Laan AC, van Amsterdam I, Tesser GI, Van Boom JH, Yeheskiel EK (1998) Synthesis of chirally pure ornithine-based PNA analogues. Nucleosides Nucleotides 17:219–231
Zatsepin TS, Romanova EA, Stetsenko DA, Gait MJ, Oretskaya TS (2003) Synthesis of 2′-modified oligonucleotides containing aldehyde or ethylenediamine groups nucleosides. Nucleotides Nucleic Acids 22:1383–1385
Acknowledgments
We thank Prof. Antonio Roviello and Dr. Valentina Roviello for their precious suggestions, and Mr. Leopoldo Zona for his invaluable technical assistance. We also thank Consiglio Nazionale delle Ricerche (CNR) for the research grant received under the bilateral CNR, Italy—SRNSF, Georgia research Program (2012–2013).
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Roviello, G.N., Musumeci, D., Bucci, E.M. et al. Synthesis of a diaminopropanoic acid-based nucleoamino acid and assembly of cationic nucleopeptides for biomedical applications. Amino Acids 43, 2537–2543 (2012). https://doi.org/10.1007/s00726-012-1335-6
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DOI: https://doi.org/10.1007/s00726-012-1335-6