Atomic Scale Structure of Self-Assembled Lipidated Peptide Nanomaterials.

ß-Peptides have great potential as novel biomaterials and therapeutic agents, due to their unique ability to self-assemble into low dimensional nanostructures, and their resistance to enzymatic degradation in vivo. However, the self-assembly mechanisms of ß-peptides, which possess increased flexibility due to the extra backbone methylene groups present within the constituent ß-amino acids, are not well understood due to inherent difficulties of observing their bottom-up growth pathway experimentally. A computational approach is presented for the bottom-up modelling of the self-assembled lipidated ß3-peptides, from monomers, to oligomers, to supramolecular low-dimensional nanostructures, in all-atom detail. The approach is applied to elucidate the self-assembly mechanisms of recently discovered, distinct structural morphologies of low dimensional nanomaterials, assembled from lipidated ß3-peptide monomers. The resultant structures of the nanobelts and the twisted fibrils are stable throughout subsequent unrestrained all-atom molecular dynamics simulations, and these assemblies display good agreement with the structural features obtained from X-ray fiber diffraction and atomic force microscopy data. This is the first reported, fully-atomistic model of a lipidated ß3-peptide-based nanomaterial, and the computational approach developed here, in combination with experimental fiber diffraction analysis and atomic force microscopy, will be useful in elucidating the atomic scale structure of self-assembled peptide-based and other supramolecular nanomaterials.

Oxy-imino saccharidic derivatives as a new structural class of aldose reductase inhibitors endowed with anti-oxidant activity.

Aldose reductase is a key enzyme in the development of long term diabetic complications and its inhibition represents a viable therapeutic solution for people affected by these pathologies. Therefore, the search for effective aldose reductase inhibitors is a timely and pressing challenge. Herein we describe the access to a novel class of oxyimino derivatives, obtained by reaction of a 1,5-dicarbonyl substrate with O-(arylmethyl)hydroxylamines. The synthesised compounds proved to be active against the target enzyme. The best performing inhibitor, compound (Z)-8, proved also to reduce both cell death and the apoptotic process when tested in an in vitro model of diabetic retinopathy made of photoreceptor-like 661w cell line exposed to high-glucose medium, counteracting oxidative stress triggered by hyperglycaemic conditions.