New Unnatural Boron-Containing Amino Acids and Peptides as Potential Delivery Agents for Neutron Capture Therapy

  • Iwona M. Wyzlic
  • John C. Beeson
  • Albert H. Soloway
  • Jinghong Yong
  • Rolf F. Barth


Since Boron Neutron Capture Therapy is to be used in the treatment of primary and metastatic brain tumors, it is essential that the boron compounds be capable of crossing the blood-brain barrier (BBB) prior to their incorporation into tumor cells. It has been shown1 that derivatives of L-phenylalanine are transported across the BBB by neutral amino acid transport system. Recently, a method has been developed to deliver low molecular weight peptides into brain.2 These observations suggest that boronated analogues of phenylalanine itself and their peptides modified by replacing aromatic amino acids with highly lipophilic, carborane-containing amino acids might be used to reach and become incorporated into brain tumor cells protected by BBB.


Aromatic Amino Acid Boron Neutron Capture Therapy Metastatic Brain Tumor Benzyl Ester Brain Tumor Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    G.J. Goldenberg, H.-Y.P. Lam and A. Begleiter. Active carrier-mediated transport of melphalan by two separate amino acid transport systems in LPC-1 plasmacytoma cells in vitro. J. Biol. Chem. 254: 1057 1064, 1979.Google Scholar
  2. 2.
    N. Bodor, L. Prokai, W.-M. Wu, H. Farag, S. Jonalagadda, M. Kawamura and J. Simpkins, A strategy for delivering peptides into the central nervous system by sequential metabolism. Science 257: 1698–1670; 1992.PubMedCrossRefGoogle Scholar
  3. 3.
    I.M. Wyzlic, A.H. Soloway, A general, convenient way to carborane-containing amino acids for boron neutron capture therapy. Tetrahedron Letters 33: 7489–7490; 1992.CrossRefGoogle Scholar
  4. 4.
    J. Coderre, unpublished results.Google Scholar
  5. 5.
    J.L. Fauchere, K.Q. Do, P.Y.C. Jow and C. Hansch, Unusually strong lipophilicity of “fat” or “super” amino-acids, including a new reference value for glycine. Erperientia 36: 1203–1204, 1980.CrossRefGoogle Scholar
  6. 6.
    P. Lindstrom, A. Gogoli, P. Rousell and S. Sjoberg, Self-degradation of ocarboranylalanine to the corresponding diastereomeric nido-analogues in acidic milieu. BUSA IF-Workshop on Boron Chemistry, Syracuse, July 1994.Google Scholar
  7. 7.
    W. Fischli, O. Leukart and R. Schwyzer, Hormone-receptor interactions. Carboranylalanine (Car) as a phenylalanine analogue: reactions with chymotrypsin. Hely. Chin. Acta 60: 959 963, 1977.Google Scholar
  8. 8.
    A. Eberle, O. Leukart, P. Schiller, J.-L. Fauchere and R. Schwyzer, Hormone-receptor interactions: [4-carboranylalanine, 5-leucine]enkephalin as a structural probe for the opiate receptor. FEBS Letters 82: 325–328, 1977.PubMedCrossRefGoogle Scholar
  9. 9.
    E. Escher, G. Guillemette, O. Leucart and D. Regoli, Pharmacological properties of two analogues of angiotensin II containing carboranylalanine (Car). Eur: J. Pharmacol. 66: 267–272, 1980.CrossRefGoogle Scholar
  10. 10.
    R. Couture, J.-N. Drouin, O. Leucart and D. Regoli, Biological activities of kinins and substance P (4–11) in which phenylalanine residues have been replaced with L-carboranylalanine. Can. J. Phvsiol. Pharnacol. 57: 1437–1442, 1979.CrossRefGoogle Scholar
  11. 11.
    a) M. Node, K. Nishide, M. Sai, K. Fuji and E. Fugita, Hard acid and soft nucliophile systems. 3. dealkylation of esters with aluminum halide-sulfide systems. J. Oro. Chem. 46:1991–1993, 1981, b) T. Tsuji, T. Kataoka, M. Yoshioka, Y. Sendo, Y. Nishitani, S. Hirai, T. Maeda and W. Nagata, Synthetic studies on b-lactam antibiotics. VII. Mild removal of the benzyl ester protecting group with aluminum trichloride. Tetrahedron Letters 30: 2793–2796, 1979.Google Scholar
  12. 12.
    T.W. Greene, and G.M. Wuts, “Protective Groups in Organic Synthesis, 2nd edition” John Wiley and Sons, Inc., New York, 1991, pp. 449–452.Google Scholar
  13. 13.
    All new compounds were characterized by 1H NMR, i’C NMR and MS. Reported yields are for homogenous samples.Google Scholar
  14. 14.
    H. R. Kricheldorf and M. Fehrle, Uber einfuhrung and abspaltung der 2- nitrophenylsulfenylschutzgruppe bei aminosauren and oligiopeptiden. Srnthesi.s 422–424, 1974.Google Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Iwona M. Wyzlic
    • 1
  • John C. Beeson
    • 1
  • Albert H. Soloway
    • 1
  • Jinghong Yong
    • 1
  • Rolf F. Barth
    • 1
  1. 1.The Ohio State UniversityColumbusUSA

Personalised recommendations