The use of molecular editing in the elucidation of the mechanism of action of amphotericin B is presented. A modular strategy for the synthesis of amphotericin B and its designed analogues is developed, which relies on an efficient gram-scale synthesis of various subunits of amphotericin B. A novel method for the coupling of the mycosamine to the aglycone was identified. The implementation of the approach has enabled the preparation of 35-deoxy amphotericin B methyl ester. Investigation of the antifungal activity and efflux-inducing ability of this amphotericin B congener provided new clues to the role of the 35-hydroxy group and is consistent with the involvement of double barrel ion channels in causing electrolyte efflux.
When measuring the properties of fluids from biological sources, sample volumes in the micro-liter range are often desired as higher volumes may not be available or are very expensive. Miniaturized viscosity and density sensors based on a vibrating cantilever fulfill this requirement. In this paper, the possibility of measuring viscosity and density of DNA solutions at the same time using such a sensor is shown. The sensor requires a sample volume of 10 μl. By doing a titration of a solution containing 110 bp long strands of DNA in the diluted, Newtonian regime, the intrinsic viscosity can be determined to be 0.047 ml mg(-1) using the cantilever sensor. The cantilever is also tested with solutions of 10 kbp long strands with concentrations in the semi-dilute, non-Newtonian regime. The comparably small change in resonance frequency and damping observed using these solutions at 12.5 kHz is attributed to shear thinning, which is expected when extrapolating results from other groups.
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