A Pyrimido-Quinoxaline Fused Heterocycle Lights Up Transfer RNA upon Binding at the Mg2+ Binding Site.

Transfer RNAs (tRNAs) are fundamental molecules in cellular translation. In this study we have highlighted a fluorescence-based perceptive approach for tRNAs by using a quinoxaline small molecule. We have synthesised a water-soluble fluorescent pyrimido-quinoxaline-fused heterocycle containing a mandatory piperazine tail (DS1) with a large Stokes shift (∼160 nm). The interaction between DS1 and tRNA results in significant fluorescence enhancement of the molecule with Kd ∼5 µM and multiple binding sites. Our work reveals that the DS1 binding site overlaps with the specific Mg2+ ion binding site in the D loop of tRNA. As a proof-of-concept, the molecule inhibited Pb2+ -induced cleavage of yeast tRNAPhe in the D loop. In competitive binding assays, the fluorescence of DS1-tRNA complex is quenched by a known tRNA-binder, tobramycin. This indicates the displacement of DS1 and, indeed, a substantiation of specific binding at the site of tertiary interaction in the central region of tRNA. The ability of compound DS1 to bind tRNA with a higher affinity compared to DNA and single-stranded RNA offers a promising approach to developing tRNA-based biomarker diagnostics in the future.

Methotrexate iontophoresis versus coal tar ointment in palmoplantar psoriasis: A pilot study.

BACKGROUND: Palmoplantar psoriasis is often disabling and refractory to conventional therapy. Systemic drugs are indicated in its severe form, but side effects are a concern with their use. Methotrexate is one such systemic drug which is effective and cheap. To reduce systemic toxicity, methotrexate has been tried topically but results have been inconsistent due to poor drug penetration into the skin by passive diffusion. Iontophoresis may enhance its absorption and efficacy. AIM: To evaluate the efficacy and safety of topical methotrexate iontophoresis in comparison with coal tar ointment in the treatment of palmoplantar psoriasis. METHODS: Thirty-one patients with palmar and/or plantar psoriasis were selected for the study and 28 patients completed it. The side having more severe involvement was treated while the other palm/sole served as a control. Iontophoresis using methotrexate solution was carried out on the study palm/sole with the injectable preparation of methotrexate (50 mg/2 ml) once a week for the first 4 weeks and subsequently every two weeks, for a total of six sittings. The control palm/sole was treated with coal tar ointment on other days. Erythema, scaling, induration and fissuring scores were noted in both groups before and after treatment. RESULTS: Both study and control groups showed decreases in scores but the reduction was more in the study group, the difference being statistically significant. LIMITATIONS: Drawbacks of our study include the small sample size and the lack of follow-up. The study and control arms were not exactly matched and the study was not blinded. CONCLUSION: Methotrexate iontophoresis was safe and more effective than coal tar ointmentin palmoplantarpsoriasis.