Hydrogen-bonding behavior of amidines in helical structure.

Amidines are an isostere of the amide bond and are completely unexplored in peptide secondary structure. This study marks the first investigation of the structural implications of amidines in folded helices. Amidines were found to engage in hydrogen-bonding interactions that are compatible with helical structure.

Thioimidates provide general access to thioamide, amidine, and imidazolone peptide-bond isosteres.

Thioamides, amidines, and heterocycles are three classes of modifications that can act as peptide-bond isosteres to alter the peptide backbone. Thioimidate protecting groups can address many of the problematic synthetic issues surrounding installation of these groups. Historically, amidines have received little attention in peptides due to limitations in methods to access them.

General Installation of (4)-Imidazolone -Amide Bioisosteres Along the Peptide Backbone.

Imidazolones represent an important class of heterocycles present in a wide range of pharmaceuticals, metabolites, and bioactive natural products and serve as the active chromophore in green fluorescent protein. Recently, imidazolones have received attention for their ability to act as a nonaromatic amide bond bioisotere which improves pharmacological properties. Herein, we present a tandem amidine installation and cyclization with an adjacent ester to yield (4)-imidazolone products.

Finding the best location: Improving the anti-amyloid ability of ruthenium(III) complexes with pyridine ligands.

Alzheimer's disease (AD) is a devastating neurological disorder where one of the primary pathological hallmarks are aggregate deposits of the peptide amyloid-beta (Aβ). Although the Food and Drug Administration (FDA) has recently approved therapeutics that specifically target Aβ, resulting in the removal of these deposits, the associated costs of such treatments create a need for effective, yet cheaper, alternatives. Metal-based compounds are propitious therapeutic candidates as they exploit the metal-binding properties of Aβ, forming stable interactions with the peptide, thereby limiting its aggregation and toxicity.

Anomeric Answer to Sulfenamide Stability and α-Nucleophilicity.

The S-N bond remains a synthetically challenging motif for organic chemists to access. The problem arises from instability in many sulfenamide derivatives, which has led to fewer S-N bond surrogate molecules compared to their hydroxylamine (NHOH) and hydrazine (NHNH) analogues. In turn, sulfenamides have often been omitted in studies regarding α-nucleophilicity.

Attached Nitrogen Test by C-N Solid-State NMR Spectroscopy for the Structure Determination of Heterocyclic Isomers.

Differentiation of heterocyclic isomers by solution H, C, and N NMR spectroscopy is often challenging due to similarities in their spectroscopic signatures. Here, C{N} solid-state NMR spectroscopy experiments are shown to operate as an "attached nitrogen test", where heterocyclic isomers are easy to distinguish based on one-dimensional nitrogen-filtered C solid-state NMR. We anticipate that these NMR experiments will facilitate the assignment of heterocyclic isomers during synthesis and natural product discovery.

Importance of Hydrogen Bonding: Structure-Activity Relationships of Ruthenium(III) Complexes with Pyridine-Based Ligands for Alzheimer's Disease Therapy.

Alzheimer's disease (AD) is the most common form of dementia, where one of the pathological hallmarks of AD is extracellular protein deposits, the primary component of which is the peptide amyloid-β (Aβ). Recently, the soluble form of Aβ has been recognized as the primary neurotoxic species, making it an important target for therapeutic development. Metal-based drugs are promising candidates to target Aβ, as the interactions with the peptide can be tuned by ligand design.