Charge‐Compensated Metallacarborane Building Blocks for Conjugation with Peptides

Abstract

The cobalt bis(dicarbollide) complex [commo-3,3'-Co(1,2-C2 B9 H11 )2 ](-) has captured much attention in biochemical and medical contexts, in particular for the treatment of tumors by boron neutron capture therapy (BNCT). Derivatives of cobalt bis(dicarbollide) are commonly prepared through ring-opening reactions of cyclic oxonium ions, so the corresponding products are usually charged. Furthermore, attempts to incorporate cobalt bis(dicarbollide) into peptides are rare, despite obvious potential advantages. Here the synthesis of an imidazolium-based charge-compensated cobalt bis(dicarbollide) building block, which allows additional modifications with moieties of biochemical relevance, such as monosaccharides, is reported. Furthermore, conjugates of these building blocks with the Y1 -receptor-selective derivative of neuropeptide Y ([F(7) ,P(34) ]-NPY) retained excellent response to hY1 receptors found to be overexpressed in breast tumors and metastases.

Methylsulfanyl‐Stabilized Rotamers of Cobalt Bis(dicarbollide)

“…The first one is the substitution of hydrogen atoms in the parent [ -by alkylation of the dimercapto derivative with various alkylating agents was reported recently. [19] This approach can also be applied to the synthesis of the corresponding bis(methylsulfanyl) derivative [8,8′-(MeS) 2 -3,3′-Co(1,2-C 2 B 9 H 10 ) 2 ] -. However, it cannot be extended to other transition-metal bis(dicarbollides) or the preparation of complexes with asymmetrically substituted dicarbollide ligands.…”

“…Topological analysis of the electron-density distribution function ρ(r) was performed with the AIMALL [42] program package with the wave function obtained by the BP86 calculations. The energies of noncovalent intramolecular interactions were calculated from the correlation between the binding energy (E int ) and the value of the potential-energy density function V C (r) at the corresponding critical point (3, -1): E int = 0.5V C (r), [18,19] which was proved to be reliable for the analysis of different types of noncovalent interactions. [24,43,44] Electrochemistry: In all of the experiments, N 2 -saturated solutions of the compound under study were used with [Bu 4 N][PF 6 ] (0.2 M) as the supporting electrolyte (Fluka, electrochemical grade) and freshly distilled CH 3 CN.…”

Targeting of peptide‐binding receptors on cancer cells with peptide‐drug conjugates

“…In a third study, a deoxygalactosyl‐functionalized, charge‐compensated cobalt bis(dicarbollide) building block with enhanced hydrophilicity was conjugated to Lys 4 in [F 7 ,P 34 ]‐NPY and a retained hY 1 R activity for the conjugate was observed. [ 268 ] [F 7 ,P 34 ]‐NPY conjugates with a maximized boron loading were also developed. [ 269,270 ] A galactosyl‐ meta‐ carborane facilitated the generation of a peptide with eight incorporated carborane clusters, that is, 80 boron atoms per peptide molecule.…”

Friedrich‐Löffler‐Preis: D. Segets / Toray Science and Technology Prize: S. Kobayashi / Inhoffen‐Medaille: T. Carell / Leipziger Wissenschaftspreis: A. G. Beck‐Sickinger / Nenitzescu‐Criegee‐Vorlesung: E. Hey‐Hawkins / Humboldt‐, Siemens‐ und Bessel‐Forschungspreise / Neue Mitglieder deutscher Wissenschaftsakademien

“…Ihre Veröffentlichung über den Einsatz eines nido ‐Dicarbaboratclusters zur Inhibierung von Cyclooxygenase‐2 wurde auf dem Titelbild von ChemMedChem präsentiert . Vor kurzem erschien eine gemeinsame Arbeit von Beck‐Sickinger und Hey‐Hawkins über Metallacarboran‐Bausteine für die Konjugation mit Peptiden in ChemBioChem …”