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In this study, the triplet-state properties of BChl a in the Fenna-Matthews-Olson (FMO) light-harvesting complex were interrogated in the absence and presence of PscB, a subunit of the Cba. tepidum reaction center (RC), at room temperature and at 77 K. Application of nanosecond time-resolved transient absorption spectroscopy supports a model in which the pathway of the triplet excitation decay within FMO has two phases, with a fast lifetime of 2.58 μs (0.57 μs at 77 K) and a slow lifetime of 44.8 μs (44.1 μs at 77 K) in the FMO-only sample. Reconstitution of PscB and FMO, however, alters the spectral signatures of BChl a excitons uniquely at 815 nm in the steady-state spectrum at 77 K. Additionally, the triplet-state lifetime of BChl a in the FMO-PscB complex shortens by almost 40% to 28.1 μs at 77 K. The two FMO trimers asymmetrically interfacing with the homodimeric RC wire excitation energy from the chlorosome to the latter. Our data supports that the single central PscB, besides its redox active roles as the electron mediators to ferredoxin, is highly plausibly involved in fine-tuning the asymmetric excitation energy transfer from two branches of FMO to the RC in green sulfur bacteria. 

Simultaneous delivery of small molecules and nucleic acids using a single vehicle can lead to novel combination treatments and multifunctional carriers for a variety of diseases. In this study, we report a novel library of aminoglycoside-derived lipopolymers nanoparticles (LPNs) for the simultaneous delivery of different molecular cargoes including nucleic acids and small-molecules. The LPN library was screened for transgene expression efficacy following delivery of plasmid DNA, and lead LPNs that showed high transgene expression efficacies were characterized using hydrodynamic size, zeta potential, 1 H NMR and FT-IR spectroscopy, and transmission electron microscopy. LPNs demonstrated significantly higher efficacies for transgene expression than 25 kDa polyethyleneamine (PEI) and lipofectamine, including in presence of serum. Self-assembly of these cationic lipopolymers into nanoparticles also facilitated the delivery of small molecule drugs ( e.g. doxorubicin) to cancer cells. LPNs were also employed for the simultaneous delivery of the small-molecule histone deacetylase (HDAC) inhibitor AR-42 together with plasmid DNA to cancer cells as a combination treatment approach for enhancing transgene expression. Taken together, our results indicate that aminoglycoside-derived LPNs are attractive vehicles for simultaneous delivery of imaging agents or chemotherapeutic drugs together with nucleic acids for different applications in medicine and biotechnology. 

Vaccines derived from chimpanzee adenovirus Y25 (ChAdOx1), human adenovirus type 26 (HAdV-D26), and human adenovirus type 5 (HAdV-C5) are critical in combatting the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic. As part of the largest vaccination campaign in history, ultrarare side effects not seen in phase 3 trials, including thrombosis with thrombocytopenia syndrome (TTS), a rare condition resembling heparin-induced thrombocytopenia (HIT), have been observed. This study demonstrates that all three adenoviruses deployed as vaccination vectors versus SARS-CoV-2 bind to platelet factor 4 (PF4), a protein implicated in the pathogenesis of HIT. We have determined the structure of the ChAdOx1 viral vector and used it in state-of-the-art computational simulations to demonstrate an electrostatic interaction mechanism with PF4, which was confirmed experimentally by surface plasmon resonance. These data confirm that PF4 is capable of forming stable complexes with clinically relevant adenoviruses, an important step in unraveling the mechanisms underlying TTS.