AbstractThe reaction of Re(CO)5Br with deprotonated 1Hâ(5â(2,2â˛:6â˛,2â˛â˛âterpyridine)pyridâ2âyl)tetrazole yields a triangular assembly formed by tricarbonyl Re(I) vertices. Photophysical measurements re Show more
AbstractThe reaction of Re(CO)5Br with deprotonated 1Hâ(5â(2,2â˛:6â˛,2â˛â˛âterpyridine)pyridâ2âyl)tetrazole yields a triangular assembly formed by tricarbonyl Re(I) vertices. Photophysical measurements reveal blueâgreen emission with a maximum at 520 nm, 32 % quantum yield, and 2430 ns longâlived excited state decay lifetime in deaerated dichloromethane solution. Coordination of lanthanoid ions to the terpyridine units redâshifts the emission to 570 nm and also reveals efficient (90 %) and fast sensitisation of both Eu(III) and Yb(III) at room temperature, with a similar rate constant kET on the order of 107 sâ1. Efficient sensitisation of Eu(III) from Re(I) is unprecedented, especially when considering the close proximity in energy between the donor and acceptor excited states. On the other hand, comparative measurements at 77 K reveal that energy transfer to Yb(III) is two orders of magnitude slower than that to Eu(III). A twoâstep mechanism of sensitisation is therefore proposed, whereby the rateâdetermining step is a thermally activated energy transfer step between the Re(I) centre and the terpyridine functionality, followed by rapid energy transfer to the respective Ln(III) excited states. At 77 K, the direct Re(I) to Eu(III) energy transfer seems to proceed via a ligandâmediated superexchange Dexterâtype mechanism. Show less
Developing novel therapeutics often follows three steps: target identification, design of strategies to suppress target activity and drug development to implement the strategies. In this review, we re Show more
Developing novel therapeutics often follows three steps: target identification, design of strategies to suppress target activity and drug development to implement the strategies. In this review, we recount the evidence identifying the basic leucine zipper transcription factors ATF5, CEBPB, and CEBPD as targets for brain and other malignancies. We describe strategies that exploit the structures of the three factors to create inhibitory dominant-negative (DN) mutant forms that selectively suppress growth and survival of cancer cells. We then discuss and compare four peptides (CP-DN-ATF5, Dpep, Bpep and ST101) in which DN sequences are joined with cell-penetrating domains to create drugs that pass through tissue barriers and into cells. The peptide drugs show both efficacy and safety in suppressing growth and in the survival of brain and other cancers in vivo, and ST101 is currently in clinical trials for solid tumors, including GBM. We further consider known mechanisms by which the peptides act and how these have been exploited in rationally designed combination therapies. We additionally discuss lacunae in our knowledge about the peptides that merit further research. Finally, we suggest both short- and long-term directions for creating new generations of drugs targeting ATF5, CEBPB, CEBPD, and other transcription factors for treating brain and other malignancies. Show less