Six fungal metabolites,
of which five were new, including one (1) with a dioxa[4.3.3]propellane
ring system, were discovered,
identified, and structurally elucidated from Neosetophoma sp. (strain MSX50044); these compounds are similar to the bis-tropolone,
eupenifeldin. Three of the meroterpenoids are potent cytotoxic agents
against breast, ovarian, mesothelioma, and lung cancer cells with
nanomolar IC50 values while not inducing mitochondrial
toxicity at 12.5 μM.
A longstanding goal in science and engineering is to mimic the size, structure, and functionality present in biology with synthetic analogs. Today, synthetic globular polymers of several million molecular weight are unknown, and, yet, these structures are expected to exhibit unanticipated properties due to their size, compactness, and low inter-chain interactions. Here we report the gram-scale synthesis of dendritic polymers, mega hyperbranched polyglycerols (mega HPGs), in million daltons. The mega HPGs are highly water soluble, soft, nanometer-scale single polymer particles that exhibit low intrinsic viscosities. Further, the mega HPGs are lubricants acting as interposed single molecule ball bearings to reduce the coefficient of friction between both hard and soft natural surfaces in a size dependent manner. We attribute this result to their globular and single particle nature together with its exceptional hydration. Collectively, these results set the stage for new opportunities in the design, synthesis, and evaluation of mega polymers.
Mucoadhesive polymers are of significant interest to the pharmaceutical, medical device, and cosmetic industries. Polysaccharides possessing charged functional groups, such as chitosan, are known for mucoadhesive properties but suffer from poor chemical definition and solubility, while the chemical synthesis of polysaccharides is challenging with few reported examples of synthetic carbohydrate polymers with engineered‐in ionic functionality. We report the design, synthesis, and evaluation of a synthetic, cationic, enantiopure carbohydrate polymer inspired by the structure of chitosan. These water‐soluble, cytocompatible polymers are prepared via an anionic ring‐opening polymerization of a bicyclic β‐lactam sugar monomer. The synthetic method provides control over the site of amine functionalization and the length of the polymer while providing narrow dispersities. These well‐defined polymers are mucoadhesive as documented in single‐molecule scale (AFM), bulk solution phase (FRAP), and ex vivo tissue experiments. Polymer length and functionality affects bioactivity as long, charged polymers display higher mucoadhesivity than long, neutral polymers or short, charged polymers.
We describe an electrochemical strategy to transduce allosteric transcription factor (aTF) binding affinity to sense steroid hormones. Our approach utilizes square wave voltammetry (SWV) to monitor changes in current output as a progesterone (PRG) specific aTF (SRTF1) unbinds from the cognate DNA sequence in the presence of PRG. The sensor detects PRG in artificial urine samples with sufficient sensitivity suitable for clinical applications. Our results highlight the capability of using aTFs as the biorecognition elements to develop electrochemical point-of-care biosensors for detection of small molecule biomarkers and analytes.
CONFLICT OF INTERESTKS, RB, CG, CMK, JEG, and MWG are inventors on a patent describing this technology filed by Boston University, which is available for license.
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