Sulfonated Pyrene as a Photoregulator for Single-Stranded DNA Looping.

Controlling the conformation and function of biomolecules through photoregulators holds great promise as a spatiotemporally controllable tool for disease control. In addition, introducing photoregulators into biomolecules has also found applications in constructing smart nanomaterials. In spite of the astonishing advances that have been made in the past few years, realizing highly controllable and efficient regulation over the conformation and function of biomolecules under physiological conditions is still challenging. Herein, sulfonated pyrene SPy was synthesized and used as a photoregulator to control the looping of single-stranded DNAs (ssDNAs) in aqueous solution. Due to its water solubility, SPy merits use in the study of biomolecules in aqueous solution. The looping of the doubly SPy-modified ssDNAs is stimulated by irradiation and regulated by SPy. Photoionization generates the radical cation of SPy (SPy.+ ). The association of SPy.+ with its neutral counterpart, SPy, gives rise to the dimer radical cation of SPy (SPy2 .+ ). During the association process, the stabilization energy released to form SPy2 .+ provides a driving force for the looping of ssDNAs. Conversely, the formed loop conformations were trapped by the formation of SPy2 .+ , and this allowed the looping dynamics to be investigated. The results reported herein suggest potential of SPy as a photoregulator for controlling the conformation and function of biomolecules under physiological conditions.

Proton Transfer Accompanied by the Oxidation of Adenosine.

Despite numerous experimental and theoretical studies, the proton transfer accompanying the oxidation of 2'-deoxyadenosine 5'-monophosphate 2'-deoxyadenosine 5'-monophosphate (5'-dAMP, A) is still under debate. To address this issue, we have investigated the oxidation of A in acidic and neutral solutions by using transient absorption (TA) and time-resolved resonance Raman (TR3 ) spectroscopic methods in combination with pulse radiolysis. The steady-state Raman signal of A was significantly affected by the solution pH, but not by the concentration of adenosine (2-50 mm). More specifically, the A in acidic and neutral solutions exists in its protonated (AH+ (N1+H+ )) and neutral (A) forms, respectively. On the one hand, the TA spectral changes observed at neutral pH revealed that the radical cation (A.+ ) generated by pulse radiolysis is rapidly converted into A. (N6-H) through the loss of an imino proton from N6. In contrast, at acidic pH (<4), AH.2+ (N1+H+ ) generated by pulse radiolysis of AH+ (N1+H+ ) does not undergo the deprotonation process owing to the pKa value of AH.2+ (N1+H+ ), which is higher than the solution pH. Furthermore, the results presented in this study have demonstrated that A, AH+ (N1+H+ ), and their radical species exist as monomers in the concentration range of 2-50 mm. Compared with the Raman bands of AH+ (N1+H+ ), the TR3 bands of AH.2+ (N1+H+ ) are significantly down-shifted, indicating a decrease in the bond order of the pyrimidine and imidazole rings due to the resonance structure of AH.2+ (N1+H+ ). Meanwhile, A. (N6-H) does not show a Raman band corresponding to the pyrimidine+NH2 scissoring vibration due to diprotonation at the N6 position. These results support the final products generated by the oxidation of adenosine in acidic and neutral solutions being AH.2+ (N1+H+ ) and A. (N6-H), respectively.

Safety and efficacy of treatment with liposomal amphotericin B in elderly patients at least 65 years old with hematological diseases.

The safety and efficacy of treatment with liposomal amphotericin B (L-AMB) in elderly patients has not been clarified, especially in Japanese patients. Therefore, we retrospectively analyzed 33 elderly patients with hematological diseases of at least 65 years old who received L-AMB between 2009 and 2012. Their clinical outcomes were compared to those of 21 patients who were younger than 65 years. L-AMB was administered for empirical therapy (n = 2) or target therapy for possible (n = 14) or probable/proven (n = 17) invasive fungal infection. There was no discontinuation of L-AMB due to adverse events. More than 2-fold increases from the baseline Cre, AST, and ALT values were observed in 21.2%, 39.4%, and 45.5% of the older group and 38.1%, 61.9%, and 52.4% of the younger group, respectively. The concurrent use of nephrotoxic antibiotics was the only risk factor for the development of a 2-fold increase in the serum Cre level. The duration of L-AMB was significantly longer in patients who developed grade III-IV hypokalemia. A partial or complete response was observed in 54.8% and 62.5% of the elderly and younger groups, respectively. In conclusion, L-AMB therapy appeared to be acceptably safe as empirical therapy or treatment for invasive fungal infection.