title: closo-borane conjugated regulatory peptides retain high biological affinity: synthesis of closo-borane conjugated Tyr(3)-octreotate derivatives for BNCT.
abstract: Despite the improvements in cancer therapy during the past years, high-grade gliomas and many other types of cancer are still extremely resistant to current forms of therapy. Boron neutron capture therapy (BNCT) provides a promising way to destroy cancer cells without damaging healthy tissue. However, BNCT in practice is still limited due to the lack of boron-containing compounds that selectively deliver boron to cancer cells. Since many neuroendocrine tumors show an overexpression of the somatostatin receptor, it was our aim to synthesize compounds that contain a large number of boron atoms and still show high affinity toward this transmembrane receptor. The synthetic peptide Tyr (3)-octreotate (TATE) was chosen as a high-affinity and internalizing tumor targeting vector (TTV). Novel boron cluster compounds, containing 10 or 20 boron atoms, were coupled to the N-terminus of TATE. The obtained affinity data demonstrate that the use of a spacer between TATE and the closo-borane moiety is the option to avoid a loss of biological affinity of closo-borane conjugated TATE. For the first time, it was shown that closo-borane conjugated regulatory peptides retain high biological affinity and selectivity toward their transmembrane tumor receptors. The results obtained and the improvement of spacer and boron building block chemistry may stimulate new directions for BNCT.
authors: Institute of Nuclear Chemistry, University of Mainz, Fritz-Strassmann-Weg 2, 55128 Mainz, Germany.
authors: Thomas
authors: T
authors: Betzel
authors: Tobias
authors: T
authors: Hess
authors: Beatrice
authors: B
authors: Waser
authors: Jean-C
authors: JC
authors: Reubi
authors: Frank
authors: F
authors: Roesch
mesh_terms: D000818:Animals; D001665:Binding Sites; D001880:Boranes / Q000138:chemical synthesis* / Q000378:metabolism / Q000627:therapeutic use; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D016466:CHO Cells; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D001880:Boranes; D010456:Peptides, Cyclic; C470036:octreotate, Tyr(3)-