Stapled peptides as potential therapeutics for diabetes and other metabolic diseases.

The field of peptide drug research has experienced notable progress, with stapled peptides featuring stabilized α-helical conformation, emerging as a promising field. These peptides offer enhanced stability, cellular permeability, and binding affinity and exhibit potential in the treatment of diabetes and metabolic disorders. Stapled peptides, through the disruption of protein-protein interactions, present varied functionalities encompassing agonism, antagonism, and dual-agonism.

The impact of E3 ligase choice on PROTAC effectiveness in protein kinase degradation.

Proteolysis targeting chimera (PROTACs) provide a novel therapeutic approach that is revolutionizing drug discovery. The success of PROTACs largely depends on the combination of their three fragments: E3 ligase ligand, linker and protein of interest (POI)-targeting ligand. We summarize the pivotal significance of the precise combination of the E3 ligase ligand with the POI-recruiting warhead, which is crucial for the successful execution of cellular processes and achieving the desired outcomes.

Rational design, optimization, and biological evaluation of novel α-Phosphonopropionic acids as covalent inhibitors of Rab geranylgeranyl transferase.

Rab geranylgeranyltransferase (GGTase-II, RGGT) catalyses the post-translational modification of eukaryotic Rab GTPases, proteins implicated in several pathologies, including cancer, diabetes, neurodegenerative, and infectious diseases. Thus, RGGT inhibitors are believed to be a potential platform for the development of drugs and tools for studying processes related to the abnormal activity of Rab GTPases. Here, a series of new α-phosphonocarboxylates have been prepared in the first attempt of rational design of covalent inhibitors of RGGT derived from non-covalent inhibitors.

Synthesis of the 6-Substituted Imidazo[1,2-a]Pyridine-3-yl-2- Phosphonopropionic Acids as Potential Inhibitors of Rab Geranylgeranyl Transferase.

Twelve phosphonopropionates derived from 2-hydroxy-3-imidazo[1,2-]pyridin-3--2-phosphonopropionic acid (3-IPEHPC) were synthesized and evaluated for their activity as inhibitors of protein geranylgeranylation. The nature of the substituent in the C6 position of imidazo[1,2-]pyridine ring was responsible for the compound's activity against Rab geranylgeranyl transferase (RGGT). The most active inhibitors disrupted Rab11A prenylation in the human cervical carcinoma HeLa cell line.

Effect of Metal-Ligand Coordination Complexes on Molecular Dynamics and Structure of Cross-Linked Poly(dimethylosiloxane).

Poly(dimethylosiloxane) (PDMS) cross-linked by metal-ligand coordination has a potential functionality for electronic devices applications. In this work, the molecular dynamics of bipyridine (bpy)-PDMS-MeCl (Me: Mn, Fe, Ni, and Zn) are investigated by means of broadband dielectric spectroscopy and supported by differential scanning calorimetry and density functional theory calculations. The study of molecular motions covered a broad range of temperatures and frequencies and was performed for the first time for metal-ligand cross-linked PDMS.

The McKenna reaction - avoiding side reactions in phosphonate deprotection.

The McKenna reaction is a well-known and popular method for the efficient and mild synthesis of organophosphorus acids. Bromotrimethylsilane (BTMS) is the main reagent in this reaction, which transforms dialkyl phosphonate esters into bis(trimethylsilyl)esters, which are then easily converted into the target acids. However, the versatile character of the McKenna reaction is not always used to its full extent, due to formation of side products.

Functionalization of the imidazo[1,2-]pyridine ring in α-phosphonoacrylates and α-phosphonopropionates via microwave-assisted Mizoroki-Heck reaction.

A series of new phosphonocarboxylates containing an imidazo[1,2-]pyridine ring has been synthesized via the microwave-assisted Mizoroki-Heck reaction. The efficient modification of the imidazo[1,2-]pyridine ring has been achieved as late-stage functionalization, enabling and accelerating the generation of a library of compounds from a common precursor.