Exploration of piperidine 3D fragment chemical space: synthesis and 3D shape analysis of fragments derived from 20 regio- and diastereoisomers of methyl substituted pipecolinates. | LitMetric
Fragment-based drug discovery is now widely adopted for lead generation in the pharmaceutical industry. However, fragment screening collections are often predominantly populated with flat, 2D molecules. Herein, we report the synthesis of piperidine-based 3D fragment building blocks - 20 regio- and diastereoisomers of methyl substituted pipecolinates using simple and general synthetic methods. -Piperidines, accessed through a pyridine hydrogenation were transformed into their -diastereoisomers using conformational control and unified reaction conditions. Additionally, diastereoselective lithiation/trapping was utilised to access -piperidines. Analysis of a virtual library of fragments derived from the 20 - and -disubstituted piperidines showed that it consisted of 3D molecules with suitable molecular properties to be used in fragment-based drug discovery programs.
The A1 domain in Von Willebrand Factor (VWF) initiates coagulation through binding to platelet glycoprotein GPIbα receptors. Von Willebrand Disease (VWD)-Mutations in A1 that either impair (type 2M) or enhance (type 2B) platelet adhesion to VWF can locally destabilize and even misfold the domain. We leveraged misfolding in the gain-of-function type 2B VWD phenotype as a target, distinct from the normal conformation.
This study assessed the influence of anthropogenic short-term nutrient enrichment (hereafter enriched) effects on seagrass population dynamics (recruitment, growth rate and mortality), morphometric traits, productivity, and leaf biodiversity assemblages in the islands of Andaman and Nicobar (ANI) of India and contrasted these findings with away from these enriched areas (hereafter pristine). Seagrass (Thalassia hemprichii and Cymodocea rotundata), and sediment samples were collected in the dry season (October-May) of ANI. Reconstruction techniques, an indirect measurement of plant growth was used to derive leaf plastochrone interval (PI), i.
Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, 1316943551, Iran.
The immune system relies on a delicate balance between attacking harmful pathogens and preserving the body's own tissues, a balance maintained by immune checkpoints. These checkpoints play a critical role in preventing autoimmune diseases by restraining excessive immune responses while allowing the immune system to recognize and destroy abnormal cells, such as tumors. In recent years, immune checkpoint inhibitors (ICIs) have become central to cancer therapy, enabling the immune system to target and eliminate cancer cells that evade detection.
Background: With the elevated level of NAFLD prevalence, the incidence of diabetes, hypertension, metabolic syndrome and other diseases is also significantly elevated. GLP-1RA can exert weight loss, glucose-lowering effects and various nonglycaemic effects. However, the relationship between quantitative reduction in hepatic fat content and improvement of pancreatic islet function by GLP-1RA is unclear.
Beijing Key Laboratory of Grape Science and Enology and State Key Laboratory of Plant Diversity and Specilaty Crops, Institute of Botany, Chinese Academy of Sciences, Beijing, 100093, China; Chinese National Botany Garden, Beijing, 100093, China. Electronic address:
Transfer RNA-derived fragments (tRFs) are noncoding small RNAs derived from transfer RNAs (tRNAs) in microorganisms, animals and plants. In plants, tRFs are known to respond to environmental stimuli, including heat, oxidative stress and UV radiation; however, their specific functions in horticultural plants, such as grapevine, remain poorly understood. In this study, we used RNA-seq to identify differentially expressed genes (DEGs) in grape leaves exposed to UV-C radiation.
