Combating multiple aetiologies of Alzheimer's disease to rescue behavioural deficits.

Alzheimer's disease (AD) encompasses a range of intricate pathologies characterized by aberrant protein aggregation, atypical accumulation of metal ions, increased levels of reactive oxygen species (ROS), oxidative stress, neuroinflammation, and synaptic dysfunction. These collectively contribute to a decline in learning, memory, and cognitive abilities, broadly classified as dementia. AD accounting for most of the dementia cases remains a significant health challenge.

Cyclic dipeptide-based small molecules modulate zinc-mediated liquid-liquid phase separation of tau.

Liquid-liquid phase separation (LLPS) is a complex physicochemical phenomenon mediated by multivalent transient weak interactions among macromolecules like polymers, proteins, and nucleic acids. It has implications in cellular physiology and disease conditions like cancer and neurodegenerative disorders. Many proteins associated with neurodegenerative disorders like RNA binding protein FUS (FUsed in Sarcoma), alpha-synuclein (α-Syn), TAR DNA binding protein 43 (TDP-43), and tau are shown to undergo LLPS.

Rationally Designed Molecules Synergistically Modulate Multifaceted Aβ Toxicity, Microglial Activation, and Neuroinflammation.

Synergistic modulation of multifaceted toxicity is the key to tackle multifactorial Alzheimer's disease (AD). The etiology of AD includes amyloid β (Aβ) amyloidosis, metal ion dyshomeostasis, reactive oxygen species (ROS), oxidative stress, mitochondrial damage, and neuroinflammation. We rationally designed multifunctional modulators by integrating pharmacophores for metal chelation, antioxidant and anti-inflammatory properties, and modulation of Aβ42 aggregation on the naphthalene monoimide (NMI) scaffold.

Multifunctional molecules with a bipyridyl core ameliorate multifaceted amyloid toxicity.

A series of 2,2'-bipyridine derivatives appended with structurally unique biomolecular auxiliaries were synthesized and investigated for their ability to ameliorate multifaceted amyloid toxicity. Our results highlight the roles of the metal-chelating bipyridine core and functional auxiliaries in effectively modulating metal-independent and -dependent amyloid toxicity, and oxidative stress observed in Alzheimer's disease (AD).

Unusual Pseudopeptides: Syntheses and Structural Analyses of Ethylenediprolyl Peptides and Their Metal Complexes with Cu(II) Ion.

The synthetic unnatural amino acids and their peptides as peptidomimetics have shown remarkable structural and functional properties. In the repertoire of synthetic peptides, pseudopeptides have emerged as attractive small peptidomimetics that are capable of forming the characteristic secondary structures in the solid/solution phase, as in natural peptides. This report describes the synthesis and structural analyses of novel pseudopeptides as ethylenediprolyl () tetra/hexapeptides, comprising a chiral diaminedicarboxylate scaffold.

Cyclic Dipeptide: A Privileged Molecular Scaffold to Derive Structural Diversity and Functional Utility.

Cyclic dipeptides (CDPs) are the simplest form of cyclic peptides with a wide range of applications from therapeutics to biomaterials. CDP is a versatile molecular platform endowed with unique properties such as conformational rigidity, intermolecular interactions, structural diversification through chemical synthesis, bioavailability and biocompatibility. A variety of natural products with the CDP core exhibit anticancer, antifungal, antibacterial, and antiviral activities.

Co-solvent polarity tuned thermochromic nanotubes of cyclic dipeptide-polydiacetylene supramolecular system.

The cooperative non-covalent interactions arising from structurally integrated multiple molecules have emerged as a powerful tool for the creation of functional supramolecular structures. Herein, we constructed cyclic dipeptide (CDP)-polydiacetylene (PDA) conjugate (CDP-DA) by introducing cyclo(l-Phe-l-Lys) to the linear 10,12-pentacosadiynoic acid. Owing to extensive hydrogen bonding characteristics, together with structural chirality of cyclo(l-Phe-l-Lys) and strong π-π stacking diacetylenic template, CDP-DA generated supramolecular nanotubes.

Cyclic Dipeptide-Guided Aggregation-Induced Emission of Naphthalimide and Its Application for the Detection of Phenolic Drugs.

The development of novel aggregation-induced emission-based fluorophoric systems (AIEgens) has gained prominent importance in recent years, owing to their wide range of applications. Herein, we demonstrate the design, syntheses, and molecular architectonics of cyclic dipeptide tethered naphthalimides (CDP-NIs) to evaluate their AIEgenic properties and applications. CDPs are versatile molecular auxiliaries that form robust intermolecular hydrogen bonding and are tethered to naphthalic anhydride with the ACQ (aggregation-caused quenching) feature.

Direct/Reversible Amidation of Troponyl Alkylglycinates via Cationic Troponyl Lactones and Mechanistic Insights.

The conversion of troponyl alkylglycinate acid/ester/amide derivatives ( acid/ester/amide) into cationic troponyl lactones () in the presence of trifluoroacetic acid and their amidation with amines is described. The reversible amidation of amides, that is, the cleavage and reformation of the amide bond via is demonstrated. The direct amidation of esters with the amino group of amino acid esters/peptide esters via is achieved.

Instability of Amide Bond Comprising the 2-Aminotropone Moiety: Cleavable under Mild Acidic Conditions.

An unusual hydrolysis/solvolysis of the classical acyclic amide bond, derived from N-troponylaminoethylglycine (Traeg) and α-amino acids, is described under mild acidic conditions. The reactivity of this amide bond is possibly owed to the protonation of the troponyl carbonyl functional group. The results suggest that the Traeg amino acid is a potential candidate for protecting and caging of the amine functional group of bioactive molecules via a cleavable amide bond.