Beyond cyclosporine A: conformation-dependent passive membrane permeabilities of cyclic peptide natural products

Many cyclic peptide natural products are larger and structurally more complex than conventional small molecule drugs. Although some molecules in this class are known to possess favorable pharmacokinetic properties, there have been few reports on the membrane permeabilities of cyclic peptide natural products. Here, we present the passive membrane permeabilities of 39 cyclic peptide natural products, and interpret the results using a computational permeability prediction algorithm based on their known or calculated 3D conformations. We found that the permeabilities of these compounds, measured in a parallel artificial membrane permeability assay, spanned a wide range and demonstrated the important influence of conformation on membrane permeability. These results will aid in the development of these compounds as a viable drug paradigm

No-till farming systems for sustainable agriculture: an overview

No-till (NT) farming systems have revolutionized agriculture by improving erosion control, soil water storage, soil quality and, in many instances, yield and net farm income. The adoption of NT systems has increased at an exponential rate since the 1990s and they are now used on 12.5% of global croplands. However, while the development of NT systems has seen much success, there can be significant agronomic, economic and/or social challenges associated with their use that limit large scale worldwide adoption. In addition, where NT is not implemented as part of an integrated system that incorporates stubble retention and appropriate crop rotations to help manage weeds, diseases, pests and soil fertility, decreases in yield can be observed. A combination of research, education and good policy development to remove economic/institutional and social barriers to uptake are required to ensure the continued success of NT. In particular, the tailoring of NT farming systems according to individual locations and the introduction of some flexibility in approach to tillage management can provide an opportunity to manage some of the challenges of NT farming systems