Aviad Levin

Amino acids and short peptides modified with the 9-fluorenylmethyloxycarbonyl (Fmoc) group possess eminent self-assembly features and show distinct potential for applications due to the inherent hydrophobicity and aromaticity of the Fmoc moiety which can promote the association of building blocks. Given the extensive study and numerous publications in this field, it is necessary to summarize the recent progress concerning these important bio-inspired building blocks. Therefore, in this review, we explore the self-organization of this class of functional molecules from three aspects, i.e., Fmoc-modified individual amino acids, Fmoc-modified di- and tripeptides, and Fmoc-modified tetra- and pentapeptides. The relevant properties and applications related to cell cultivation, bio-templating, optical, drug delivery, catalytic, therapeutic and antibiotic properties are subsequently summarized. Finally, some existing questions impeding the development of Fmoc-modified simple biomolecules are discussed, and corresponding strategies and outlooks are suggested.

The transition of peptides and proteins from the solution phase into fibrillar structures is a general phenomenon encountered in functional and aberrant biology and is increasingly exploited in soft materials science. However, the fundamental molecular events underpinning the early stages of their assembly and subsequent growth have remained challenging to elucidate. Here, we show that liquid-liquid phase separation into solute-rich and solute-poor phases is a fundamental step leading to the nucleation of supramolecular nanofibrils from molecular building blocks, including peptides and even amphiphilic amino acids. The solute-rich liquid droplets act as nucleation sites, allowing the formation of thermodynamically favorable nanofibrils following Ostwald's step rule. The transition from solution to liquid droplets is entropy driven while the transition from liquid droplets to nanofibrils is mediated by enthalpic interactions and characterized by structural reorganization. These findings shed light on how the nucleation barrier toward the formation of solid phases can be lowered through a kinetic mechanism which proceeds through a metastable liquid phase.

An increasing body of evidence indicates that accumulation of soluble oligomeric assemblies of β-amyloid polypeptide (Aβ) play a key role in Alzheimer's disease (AD) pathology. Specifically, 56 kDa oligomeric species were shown to be correlated with impaired cognitive function in AD model mice. Several reports have documented the inhibition of Aβ plaque formation by compounds from natural sources. Yet, evidence for the ability of common edible elements to modulate Aβ oligomerization remains an unmet challenge. Here we identify a natural substance, based on cinnamon extract (CEppt), which markedly inhibits the formation of toxic Aβ oligomers and prevents the toxicity of Aβ on neuronal PC12 cells. When administered to an AD fly model, CEppt rectified their reduced longevity, fully recovered their locomotion defects and totally abolished tetrameric species of Aβ in their brain. Furthermore, oral administration of CEppt to an aggressive AD transgenic mice model led to marked decrease in 56 kDa Aβ oligomers, reduction of plaques and improvement in cognitive behavior. Our results present a novel prophylactic approach for inhibition of toxic oligomeric Aβ species formation in AD through the utilization of a compound that is currently in use in human diet.