Boronated Asparagine and Glutamine Analogs for BNCT

Boron Neutron Capture Therapy (BNCT) has a clear theoretical advantage over other techniquesas a method of delivering cell-killing radiation to tumors. The inability of leukemia cells to synthesizeasparagine and the requirement of exogeneous asparagine by tumor cells provide an excellentopportunity for exploitation by BNCT, using boron analogs. Boronic acids are also good inhibitors ofserine proteases and good analogs of transition states in enzymatic reactions, Boron-containing transitionstate analogs of asparagine and glutamine could use the inhibition mechanism to control tumorproliferation. Incorporation of boron into tumor cell can pave way for cell destruction by BNCT. PhaseI research will focus on the synthesis of (i) boron-containing transition state analogs of asparagine andglutamine, (ii) a delta-boronated amino acid, and evaluation of their cytotoxicity and in vitro efficacy.Phase II effort will focus on (i) synthesis of other boronated amino acid analogs and their peptides, (ii)further in vitro toxicity, in vivo efficacy studies, and (iii) BNCT, antineoplastic activity and long termtoxicity of lead compounds.