Abstract
This work deals with the Dakin–West synthesis, starting from the nucleoamino acid 1-thyminyl acetic acid, as well the NMR, ESI MS, and X-ray characterization of a heteroaromatic compound denominated by us T2CO, comprising two thymine moieties anchored to a 2-propanonic unit, the spectroscopic properties of which were studied by UV as a function of temperature and ionic strength. Preliminary binding-studies with molecules of biomedical interest such as nucleic acids and proteins, performed on samples containing T2CO, suggested that this molecule is able to interact very weakly with double-stranded RNA, whereas it does not seem to bind other nucleic acids or proteins. Moreover, by studies with fresh human serum we found that T2CO is resistant to enzymatic degradation till 24 h, whereas UV metal binding-studies, performed using solutions of copper (II) chloride dihydrate and nickel (II) chloride hexahydrate, revealed a certain ability of T2CO to bind copper (II) cation. Finally, by CD spectroscopy we investigated the influence of T2CO on the already described supramolecular networks based on l-serine-containing nucleopeptides. More particularly, we found that T2CO is able to increase the level of structuration of the non-covalent supramolecular assembly of the chiral nucleopeptides, which is a feature of remarkable interest for the development of innovative drug delivery tools.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Altomare A, Burla MC, Camalli M, Cascarano GL, Giacovazzo C, Guagliardi A, Moliterni AGG, Polidori G, Spagna R (1999) SIR97: a new tool for crystal structure determination and refinement. J Appl Cryst 32:115–119
Curran TT (1995) Implementation of the Dakin–West reaction for the preparation of an α-amino-pentafluoroethyl ketone. J Fluorine Chem 74:107–112
Dakin HD, West RA (1928) General reaction of amino acids I and II. J Biol Chem 78:91–105
Fei Z, Liu Y, Yan Z, Fan D, Alexander A, Yang JH (2009) Targeting viral dsRNA for antiviral prophylaxis. FASEB J. doi:10.1096/fj.09-144915
Kaiser C, Audia VH, Carter JP, McPherson DW, Waid PP, Lowe VC, Noronha-Blob L (1993) Synthesis and antimuscarinic activity of some 1-cycloalkyl-1-hydroxy-1-phenyl-3-(4-substituted piperazinyl)-2-propanones and related compounds. J Med Chem 36:610–616
Kawase M, Hirabayashi M, Kumakura H, Saito S, Yamamoto K (2000) The Dakin–West reaction of N-alkoxycarbonyl-N-alkyl-α-amino acids employing trifluoroacetic anhydride. Chem Pharm Bull 48:114–119
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
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
Rother A, Bobbitt JM, Schwarting AE (1962) Structure and synthesis of the alkaloid anaferine. Chem Ind (London):654–655
Roviello GN, Musumeci D, Castiglione M, Bucci EM, Pedone C, Benedetti E (2009) Solid phase synthesis and RNA-binding studies of a serum-resistant nucleo-epsilon-peptide. J Pept Sci 15:155–160
Roviello GN, Benedetti E, Pedone C, Bucci EM (2010) Nucleobase-containing peptides: an overview of their characteristic features and applications. Amino Acids 39:45–57
Roviello GN, Musumeci D, Bucci EM, Pedone C (2011) Evidences for supramolecular organization of nucleopeptides: synthesis, spectroscopic and biological studies of a novel dithymine l-serine tetrapeptide. Mol BioSyst 7:1073–1080
Sheldrick GM (1996) SADABS, Program for empirical absorption correction. University of Göttingen, Germany
Sheldrick GM (1997) SHELX-97 University of Göttingen, Germany
Tran K, Bickar D (2006) Dakin–West synthesis of β-aryl ketones. J Org Chem 71:6640–6643
Varughese S, Draper SM (2010) Solid state conformational preferences of a flexible molecular backbone derived from acetone: dependence on electron donating/withdrawing ability of substitutions. Cryst Grow Des 10:2298–2305
Acknowledgments
We thank Dr. Valentina Roviello, Dr. Giuseppe Perretta, Mr. Leopoldo Zona and Dr. Andrea Ricci for their precious suggestions and invaluable technical assistance. We are also grateful to the institutions that supported our laboratory (Consiglio Nazionale delle Ricerche and Università degli Studi di Napoli ‘Federico II’) and to C.R.d.C. “Nuove Tecnologie per le Attività Produttive” of Campania Region (Italy) for use of Bruker-Nonius X-ray equipment.
Conflict of interest
The authors state that there is no conflict of interests.
Author information
Authors and Affiliations
Corresponding author
Additional information
G. N. Roviello and G. Roviello contributed equally to this work.
Rights and permissions
About this article
Cite this article
Roviello, G.N., Roviello, G., Musumeci, D. et al. Dakin–West reaction on 1-thyminyl acetic acid for the synthesis of 1,3-bis(1-thyminyl)-2-propanone, a heteroaromatic compound with nucleopeptide-binding properties. Amino Acids 43, 1615–1623 (2012). https://doi.org/10.1007/s00726-012-1237-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00726-012-1237-7