Biochemical applications of boron cluster chemistry

Abstract

Monoclonal antibodies (Mabs) and their immunoreactive fragments continue to be attractive, but as yet unproven, vehicles for the selective delivery of therapeutic quantities of 10B to tumors for the purpose of boron neutron capture therapy (BNCT). Available chemical methodologies and boron-containing reagents for immunoprotein conjugation will be delineated along with the use of designed, precisely synthesized macromolecules which serve as “l0B-trailer” reagents for protein conjugation. The latter designed species have been investigated and are either synthetic peptide-like oligomers containing large quantities of boron in their component a-amino acids or they are hydrophilic polyamides comprised of boron-rich repeating units. Both classes of reagent are produced through solid-supported syntheses (Merrifield methodology). Use of these precisely synthesized 10B-trailer species as conjugation reagents equipped with analytically useful fluorescent labels may provide the 103 B-atoms per Mab molecule required for effective BNCT. This methodology provides Mab conjugation with a minimal loss of structural information while providing chemical reproducibility. The in vivo evaluation of this approach has led to the identification of potential improvements in the use of immunoproteins as vehicles for the selective delivery of boron (or other agents) to tumor cells. Consequently, the synthesis of a hydrophilic and boron-rich peptide which is structurally discrete and immunodirected is in progress. © 1991, IUPAC