Poster Presentation 12th Australian Peptide Conference 2017

Synthesis of L-boronophenylalnine and L-carboranylalanine bearing peptides by ribosome (#134)

Yizhen Yin 1 , Hiroaki Suga 1
  1. The University of Tokyo, Bunkyo-ku, TOKYO, Japan

Boron neutron capture therapy (BNCT) is a promising therapeutic technique for cancers by using the highly energetic 4He2+ and 7Li3+ arising from the thermal neutron capture by boron-10 (10B). It can selectively treat cancers without damaging normal cells nearby, and has focused primarily on the treatment of high grade gliomas, recurrent cancers of the head and neck region, etc. Promise for prostate, liver and breast cancers has also been shown by the ongoing researches. The primary and most important factor for successful BNCT is the development of nontoxic boron delivery agents which can selectively target tumor cells and accumulate in sufficient amounts. Although considerable efforts have been made, only disodium mercaptododecaborate (BSH) and L-boronophenylalanine (L-BPA) are being used in clinical trials. However, they are not ideal 10B carriers due to insufficient tumor selectivity and much faster clearance rate after injection. Therefore, novel and powerful 10B delivery agents are in high demand. As L-BPA has a similar structure to tyrosine, we found that L-BPA could be charged onto tRNAs by flexizyme, and expressed by means of translation machinery under the reprogrammed genetic code. L-Carboranylalanine (L-CBA) has been reported as a bioisostere of L-phenylalanine, because the dimension of carborane in L-CBA is only slightly larger than the space occupied by a benzene ring rotating about its C(l)-C(4) axis. In this paper, we also synthesized L-CBA, and successfully incorporated it into peptides by flexible in vitro translation (FIT) system. This provide novel strategies for screening of boronated peptides as BNCT agents.