β-Bracelets: Macrocyclic Cross-β Epitope Mimics Based on a Tau Conformational Strain.

The aggregation of misfolded tau into neurotoxic fibrils is linked to the progression of Alzheimer's disease (AD) and related tauopathies. Disease-associated conformations of filamentous tau are characterized by hydrophobic interactions between side chains on unique and distant β-strand modules within each protomer. Here, we report the design and diversity-oriented synthesis of β-arch peptide macrocycles composed of the aggregation-prone PHF6 hexapeptide of tau and the cross-β module specific to the AD tau fold.

Blocking tau transmission by biomimetic graphene nanoparticles.

Tauopathies are a class of neurodegenerative diseases resulting in cognitive dysfunction, executive dysfunction, and motor disturbance. The primary pathological feature of tauopathies is the presence of neurofibrillary tangles in the brain composed of tau protein aggregates. Moreover, tau aggregates can spread from neuron to neuron and lead to the propagation of tau pathology.

-Aminoglycine and Its Derivatives Stabilize PPII Secondary Structure.

The identification of unnatural residues that stabilize polyproline type 2 (PPII) folds can aid in the design of peptidomimetics targeting PPII-binding domains. Here, we examine the impact of peptide backbone N-amination on PPII helix stability and find -aminoglycine (aGly) to be an effective PPII promoter. Further derivatization of an aGly-containing peptide affords '-alkylated analogues with increased helical propensity.