RESUMEN
All-visible-light switchable diarylethene-perylenebisimide (DAE-PBI) dyads having bromine heavy atoms in the molecule were designed and synthesized. Very recently, we found a unique visible-light-induced cyclization reaction in a DAE-PBI dyad. The dyad exhibited reversible cyclization and cycloreversion reactions upon alternate irradiation with green (500-550 nm) and red (>600 nm) light. From the experimental results, it was suggested that the triplet state of DAE unit was generated via multiplicity conversion based on intramolecular energy transfer from the singlet excited state of PBI unit and that the cyclization reaction of DAE unit proceeded from the triplet state. In addition, it was revealed that the reactivity remarkably increased in a solvent containing heavy atoms such as carbon tetrachloride and iodoethane (i.e., external heavy-atom effect). Based on such results, in this study, we attempted to design and synthesize novel DAE-PBI dyads introducing bromine heavy atoms at different positions in the molecule. The synthesized dyads exhibited higher quantum yields of photocyclization reaction under visible-light irradiation even in a heavy-atom-free solvent compared to the previous dyad having no heavy atoms. The magnitude of enhancement well correlated to the contribution ratio of atomic orbital of bromine to the molecular orbital in LUMOs. These results indicated that the internal heavy atom effectively contributed to the visible-light-induced cyclization reaction in DAE-PBI dyads. Such an internal heavy-atom effect will pave the way for new molecular design to develop all-visible-light-activatable molecular switches.
RESUMEN
Three novel NY-ESO-1 CD4 T cell epitopes were identified using PBMC obtained from patients who were vaccinated with a complex of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein (CHP-NY-ESO-1). The restriction molecules were determined by antibody blocking and using various EBV-B cells with different HLA alleles as APC to present peptides to CD4 T cells. The minimal epitope peptides were determined using various N- and C-termini truncated peptides deduced from 18-mer overlapping peptides originally identified for recognition. Those epitopes were DRB1*0901-restricted NY-ESO-1 87-100, DQB1*0401-restricted NY-ESO-1 95-107 and DRB1*0803-restricted NY-ESO-1 124-134. CD4 T cells used to determine those epitope peptides recognized EBV-B cells or DC that were treated with recombinant NY-ESO-1 protein or NY-ESO-1-expressing tumor cell lysate, suggesting that the epitope peptides are naturally processed. These CD4 T cells showed a cytokine profile with Th1 characteristics. Furthermore, NY-ESO-1 87-100 peptide/HLA-DRB1*0901 tetramer staining was observed. Multiple Th1-type CD4 T cell responses are beneficial for inducing effective anti-tumor responses after NY-ESO-1 protein vaccination.