Amino Acids

, Volume 49, Issue 8, pp 1347–1353 | Cite as

Lac-l-TTA, a novel lactose-based amino acid–sugar conjugate for anti-metastatic applications

  • Giovanni N. Roviello
  • Roberta Iannitti
  • Rosanna Palumbo
  • Hayarpi Simonyan
  • Caterina Vicidomini
  • Valentina Roviello
Original Article

Abstract

Here we describe the synthesis, chromatographic purification, MS and NMR characterization of a new lactosyl-derivative, i.e. a lactosyl thiophenyl-substituted triazolyl-thione l-alanine (Lac-L-TTA). This amino acid–sugar conjugate was prepared by solution synthesis in analogy to the natural fructosyl-amino acids. Furthermore, we investigated the inhibition of PC-3 prostate cancer cell colony formation by this lactose derivative in comparison with the less polar fructose-based derivative, Fru-L-TTA. This let us to compare the properties of the artificial derivative, object of the present work, with the monosaccharide-based counterpart and to obtain a preliminary information on the influence of polarity on such biological activity. A significantly higher anticancer effect of Lac-L-TTA with respect to the fructose analogue emerged from our study suggesting that the anti-metastatic potential of fructosyl-amino acids can be enhanced by increasing the polarity of the compounds, for example by introducing disaccharide moieties in place of fructose.

Keywords

Glycated amino acid Anti-metastatic Fructosyl-amino acid Lactose 

References

  1. Campo VL, Carvalho I, Allman S, Davis BG, Field RA (2007) Chemical and chemoenzymatic synthesis of glycosyl-amino acids and glycopeptides related to Trypanosoma cruzi mucins. Org Biomol Chem 5:2645–2657CrossRefPubMedGoogle Scholar
  2. Di Fabio G, De Capua A, De Napoli L, Montesarchio D, Piccialli G, Rossi F, Benedetti E (2001) A new strategy for the solid-phase synthesis of glycoconjugate biomolecules. Synlett 3:341–344CrossRefGoogle Scholar
  3. Esposito G, Teta R, Miceli R, Ceccarelli LS, Della Sala G, Camerlingo R, Irollo E, Mangoni A, Pirozzi G, Costantino V (2015) Isolation and assessment of the in vitro anti-tumor activity of smenothiazole A and B, chlorinated thiazole containing peptide/polyketides from the Caribbean sponge, Smenospongia aurea. Mar Drugs 13:444–459CrossRefPubMedPubMedCentralGoogle Scholar
  4. Estendorfer S, Ledl F, Severin T (1990) Formation of an aminoreductone from glucose. Angew Chem Int Ed Engl 29:536–537CrossRefGoogle Scholar
  5. Gallas K, Pototschnig G, Adanitsch F, Stütz AE, Wrodnigg TM (2012) The Amadori rearrangement as glycoconjugation method: synthesis of non-natural C-glycosyl type glycoconjugates. Beilstein J Org Chem 8:1619–1629CrossRefPubMedPubMedCentralGoogle Scholar
  6. Glinsky GV, Price JE, Glinsky VV, Mossine VV, Kiriakova G, Metcalf JB (1996) Inhibition of human breast cancer metastasis in nude mice by synthetic glycoamines. Cancer Res 56:5319–5324PubMedGoogle Scholar
  7. Gruner SAW, Locardi E, Lohof E, Kessler H (2002) Carbohydrate-based mimetics in drug design: sugar amino acids and carbohydrate scaffolds. Chem Rev 102:491–514CrossRefPubMedGoogle Scholar
  8. Horikawa H, Okada M, Nakamura Y, Sato A, Iwamoto N (2002) Production of hydroxyl radicals and α-dicarbonyl compounds associated with Amadori compound-Cu 2 complex degradation. Free Radic Res 36:1059–1065CrossRefPubMedGoogle Scholar
  9. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90CrossRefPubMedGoogle Scholar
  10. Kumar V, Ramesh NG (2007) A versatile strategy for the synthesis of N-linked glycoamino acids from glycals. Org Biomol Chem 5:3847–3858CrossRefPubMedGoogle Scholar
  11. Mehlen P, Puisieux A (2006) Metastasis: a question of life or death. Nat Rev Cancer 6:449–458CrossRefPubMedGoogle Scholar
  12. Mossine VV, Chopra P, Mawhinney TP (2008) Interaction of tomato lycopene and ketosamine against rat prostate tumorigenesis. Can Res 68:4384–4391CrossRefGoogle Scholar
  13. Mottram DS (1994) Flavor compounds formed during the Maillard reaction: thermally generated flavors. Maillard Microw Extrus Process 543:104–126Google Scholar
  14. Rakosi K, Szolomajer-Csikos O, Kalmar L, Szurmai Z, Kerekgyarto J, Toth GK (2011) Synthesis of N-glycopeptides applying glycoamino acid building blocks with a combined Fmoc/Boc strategy. Protein Pept Lett 18:679–683CrossRefPubMedGoogle Scholar
  15. Risseeuw MD, Overhand M, Fleet GW, Simone MI (2007) A compendium of sugar amino acids (SAA): scaffolds, peptide- and glyco-mimetics. Tetrahedron Asymmetry 18:2001–2010CrossRefGoogle Scholar
  16. 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-γ-peptides based on diaminobutyric acid. J Pept Sci 12:829–835CrossRefPubMedGoogle Scholar
  17. 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 26:1307–1310CrossRefPubMedGoogle Scholar
  18. Roviello GN, Benedetti E, Pedone C, Bucci EM (2010a) Nucleobase-containing peptides: an overview of their characteristic features and applications. Amino Acids 39:45–57CrossRefPubMedGoogle Scholar
  19. Roviello GN, Musumeci D, De Cristofaro A, Capasso D, Di Gaetano S, Bucci EM, Pedone C (2010b) Alternate dab-aegPNAs: synthesis, nucleic acid binding studies and biological activity. Mol BioSyst 6:199–205CrossRefPubMedGoogle Scholar
  20. Roviello GN, Gaetano SD, Capasso D, Franco S, Crescenzo C, Bucci EM, Pedone C (2011a) RNA-binding and viral reverse transcriptase inhibitory activity of a novel cationic diamino acid-based peptide. J Med Chem 54:2095–2101CrossRefPubMedGoogle Scholar
  21. Roviello GN, Musumeci D, Bucci EM, Pedone C (2011b) Evidences for supramolecular organization of nucleopeptides: synthesis, spectroscopic and biological studies of a novel dithymine l-serine tetrapeptide. Mol BioSyst 7:1073–1080CrossRefPubMedGoogle Scholar
  22. Roviello GN, Vicidomini C, Di Gaetano S, Capasso D, Musumeci D, Roviello V (2016a) Solid phase synthesis and RNA-binding activity of an arginine-containing nucleopeptide. RSC Adv. 6:14140–14148CrossRefGoogle Scholar
  23. Roviello GN, Roviello V, Autiero I, Saviano M (2016b) Solid phase synthesis of TyrT, a thymine–tyrosine conjugate with poly(A) RNA-binding ability. RSC Adv. 6:27607–27613CrossRefGoogle Scholar
  24. Roviello GN, Iannitti R, Roviello V, Palumbo R, Simonyan H, Vicidomini C (2017) Synthesis and biological evaluation of a novel Amadori compound. Amino Acids. doi:10.1007/s00726-016-2363-4 Google Scholar
  25. Russo A, Aiello C, Grieco P, Marasco D (2016) Targeting “Undruggable” proteins: design of synthetic cyclopeptides. Curr Med Chem 23:748–762CrossRefPubMedGoogle Scholar
  26. Saghyan AS, Simonyan HM, Petrosyan SG, Geolchanyan AV, Roviello GN, Musumeci D, Roviello V (2014) Thiophenyl-substituted triazolyl-thione l-alanine: asymmetric synthesis, aggregation and biological properties. Amino Acids 46:2325–2332CrossRefPubMedGoogle Scholar
  27. Tai S, Sun Y, Squires JM, Zhang H, Oh WK, Liang C-Z, Huang J (2011) PC3 is a cell line characteristic of prostatic small cell carcinoma. Prostate 71:1668–1679CrossRefPubMedPubMedCentralGoogle Scholar
  28. Teta R, Irollo E, Della Sala G, Pirozzi G, Mangoni A, Costantino V (2013) Smenamides A and B, chlorinated peptide/polyketide hybrids containing a dolapyrrolidinone unit from the Caribbean sponge Smenospongia aurea. Evaluation of their role as leads in antitumor drug research. Mar Drugs 11:4451–4463CrossRefPubMedPubMedCentralGoogle Scholar
  29. Wang Y, Nangia-Makker P, Tait L, Balan V, Hogan V, Pienta KJ, Raz A (2009) regulation of prostate cancer progression by Galectin-3. Am J Pathol 174:1515–1523CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Wien 2017

Authors and Affiliations

  • Giovanni N. Roviello
    • 1
  • Roberta Iannitti
    • 1
  • Rosanna Palumbo
    • 1
  • Hayarpi Simonyan
    • 3
  • Caterina Vicidomini
    • 1
  • Valentina Roviello
    • 2
  1. 1.CNRIstituto di Biostrutture e Bioimmagini (Via Mezzocannone Site and Headquarters)NaplesItaly
  2. 2.Centro Regionale di Competenza (CRdC) TecnologieNaplesItaly
  3. 3.Institute of PharmacyYerevan State UniversityYerevanArmenia

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