Abstract
Boron neutron capture therapy (BNCT) is a binary therapy that is to select a suitable boronated drug absorbed by tumor tissue and then to give thermal neutron irradiation. By nuclear reaction of 10B with thermal neutron, high linear energy transfer (LET) radiations including α2+ and 7Li+ can be produced. If the boronated drug is able to concentrate on tumor tissue, the resulted high-LET radiations will kill tumor with sparing of the normal tissue. αvβ3 integrin is an important cell adhesion receptor involved in tumor-induced angiogenesis and tumor metastasis. The high binding specificity to αvβ3 integrins of the peptides containing Arg-Gly-Asp(RGD) residue suggests that the RGD peptides conjugated boronated compound may be developed as a potential BNCT agent. In this study, using 4-iodobenzoic acid as starting material to proceed via protection, boronation and deprotection, the boronated compound, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (TDBA) was obtained. By activation of carboxyl group, the TDBA was converted to NHS-activated ester. The aforementioned products were confirmed by 1H and 13C-NMR. While proceeding coupling reaction in the NHS-activated ester with mono-RGD peptide, or dimer-RGD peptide, high performance liquid chromatography (HPLC) was employed to separate and purify the coupling products, the boronated mono-RGD peptide and boronated dimer-RGD peptide with retention times at 14.5 min or 16.2 min, respectively. The molecular weights identified by MALDI-TOF-Mass for the boronated mono-RGD and the boronated dimmer-RGD are 885.23 Da and 1615.286 Da, respectively.