Heat-stable enterotoxin (STa), a peptide secreted by enterotoxigenic Escherichia coli , exerts potent diarrheagenic activity through guanylyl cyclase C (GC-C) activation. Owing to its structural similarity to guanylin and uroguanylin, GC-C is also selectively expressed in colorectal cancer cells, making STa an attractive scaffold for therapeutic targeting. We recently developed attenuated STa analogs with regioselective disulfide formation that retain GC-C binding while reducing toxicity, enabling applications in drug delivery. Here, we designed a novel topological isomer, Mpr 5 ,D-Lys 16 (BSH-hexanoyl)-STp(5-17), by introducing a boron-containing moiety (BSH) to serve as a 10 B neutron capture nucleus. This design aimed to enhance boron neutron capture therapy (BNCT), a next-generation radiotherapy requiring selective boron accumulation in cancer cells. The conjugate preserved the structural integrity of the STa binding motif and demonstrated selective uptake into GC-C-positive Caco-2 cells. Upon neutron irradiation, significant cell death was observed, highlighting its potential as a peptide-based boron delivery system. These findings establish attenuated STa derivatives as versatile platforms for targeted cancer therapy and open new avenues for integrating peptide engineering with BNCT.
Hidaka et al. (Sun,) studied this question.