Project description:Ammonium ions are ubiquitous in chemistry and molecular biology. Considerable efforts have been undertaken to develop synthetic receptors for their selective molecular recognition. The type of host compounds for organic ammonium ion binding span a wide range from crown ethers to calixarenes to metal complexes. Typical intermolecular interactions are hydrogen bonds, electrostatic and cation-π interactions, hydrophobic interactions or reversible covalent bond formation. In this review we discuss the different classes of synthetic receptors for organic ammonium ion recognition and illustrate the scope and limitations of each class with selected examples from the recent literature. The molecular recognition of ammonium ions in amino acids is included and the enantioselective binding of chiral ammonium ions by synthetic receptors is also covered. In our conclusion we compare the strengths and weaknesses of the different types of ammonium ion receptors which may help to select the best approach for specific applications.
Project description:Formulations and devices for precision medicine applications must be tunable and multiresponsive to treat heterogeneous patient populations in a calibrated and individual manner. We engineered modular poly(acrylamide-co-methacrylic acid) copolymers, cross-linked into multiresponsive nanogels with either a nondegradable or degradable disulfide cross-linker, that were customized via orthogonal chemistries to target biomarkers of an individual patient's disease or deliver multiple therapeutic modalities. Upon modification with functional small molecules, peptides, or proteins, these nanomaterials delivered methylene blue with environmental responsiveness, transduced visible light for photothermal therapy, acted as a functional enzyme, or promoted uptake by cells. In addition to quantifying the nanogels' composition, physicochemical characteristics, and cytotoxicity, we used a QCM-D method for characterizing nanomaterial degradation and a high-throughput assay for cellular uptake. In conclusion, we generated a tunable nanogel composition for precision medicine applications and new quantitative protocols for assessing the bioactivity of similar platforms.
Project description:Three (R)-BINOL-based macrocyclic receptors obtained via double-amidation reaction were used for chiral recognition of four anions derived from α-hydroxy and α-amino acids. The structural factors of hosts and guests that affect chiral recognition processes were also investigated, indicating that the proper geometry of both receptor and guest molecules plays a crucial role in effective enantio-discrimination.
Project description:The purpose of our review is to briefly show what different compounds of marine origin, from low molecular weight ones to peptides and proteins, offer for understanding the structure and mechanism of action of nicotinic acetylcholine receptors (nAChRs) and for finding novel drugs to combat the diseases where nAChRs may be involved. The importance of the mentioned classes of ligands has changed with time; a protein from the marine snake venom was the first excellent tool to characterize the muscle-type nAChRs from the electric ray, while at present, muscle and α7 receptors are labeled with the radioactive or fluorescent derivatives prepared from α-bungarotoxin isolated from the many-banded krait. The most sophisticated instruments to distinguish muscle from neuronal nAChRs, and especially distinct subtypes within the latter, are α-conotoxins. Such information is crucial for fundamental studies on the nAChR revealing the properties of their orthosteric and allosteric binding sites and mechanisms of the channel opening and closure. Similar data are provided by low-molecular weight compounds of marine origin, but here the main purpose is drug design. In our review we tried to show what has been obtained in the last decade when the listed classes of compounds were used in the nAChR research, applying computer modeling, synthetic analogues and receptor mutants, X-ray and electron-microscopy analyses of complexes with the nAChRs, and their models which are acetylcholine-binding proteins and heterologously-expressed ligand-binding domains.
Project description:Nanoparticle receptors were synthesized through micellar imprinting to bind glycosphingolipids with 20-140 μM binding affinities, meanwhile distinguishing glycan composition, the number of acyl chains, and hydroxylation of acyl chains in the lipids. The strong binding enabled the receptors to protect their target glycolipids dispersed in lipid membranes from enzymatic degradation.
Project description:Evolutionary science has led to many practical applications of genetic evolution but few practical uses of cultural evolution. This is because the entire study of evolution was gene centric for most of the 20th century, relegating the study and application of human cultural change to other disciplines. The formal study of human cultural evolution began in the 1970s and has matured to the point of deriving practical applications. We provide an overview of these developments and examples for the topic areas of complex systems science and engineering, economics and business, mental health and well-being, and global change efforts.
Project description:Microalbuminuria is an important clinical marker of several cardiovascular, metabolic, and other diseases such as diabetes, hypertension, atherosclerosis, and cancer. The accurate detection of microalbuminuria relies on albumin quantification in the urine, usually via an immunoturbidity assay; however, like many antibody-based assessments, this method may not be robust enough to function in global health applications, point-of-care assays, or wearable devices. Here, we develop an antibody-free approach using synthetic molecular recognition by constructing a polymer to mimic fatty acid binding to the albumin, informed by the albumin crystal structure. A single-walled carbon nanotube, encapsulated by the polymer, as the transduction element produces a hypsochromic (blue) shift in photoluminescence upon the binding of albumin in clinical urine samples. This complex, incorporated into an acrylic material, results in a nanosensor paint that enables the detection of microalbuminuria in patient samples and comprises a rapid point-of-care sensor robust enough to be deployed in resource-limited settings.
Project description:The combination of a pyrenyl tetraamine with an isophthaloyl spacer has led to two new water-soluble carbohydrate receptors ("synthetic lectins"). Both systems show outstanding affinities for derivatives of N-acetylglucosamine (GlcNAc) in aqueous solution. One receptor binds the methyl glycoside GlcNAc-β-OMe with Ka ≈20,000 m(-1), whereas the other one binds an O-GlcNAcylated peptide with Ka ≈70,000 m(-1). These values substantially exceed those usually measured for GlcNAc-binding lectins. Slow exchange on the NMR timescale enabled structural determinations for several complexes. As expected, the carbohydrate units are sandwiched between the pyrenes, with the alkoxy and NHAc groups emerging at the sides. The high affinity of the GlcNAcyl-peptide complex can be explained by extra-cavity interactions, raising the possibility of a family of complementary receptors for O-GlcNAc in different contexts.
Project description:The discovery of molecules that bind tightly and selectively to desired proteins continues to drive innovation at the interface of chemistry and biology. This paper describes the binding of human insulin by the synthetic receptor cucurbit[7]uril (Q7) in vitro. Isothermal titration calorimetry and fluorescence spectroscopy experiments show that Q7 binds to insulin with an equilibrium association constant of 1.5 × 10(6) M(-1) and with 50-100-fold selectivity versus proteins that are much larger but lack an N-terminal aromatic residue, and with >1000-fold selectivity versus an insulin variant lacking the N-terminal phenylalanine (Phe) residue. The crystal structure of the Q7·insulin complex shows that binding occurs at the N-terminal Phe residue and that the N-terminus unfolds to enable binding. These findings suggest that site-selective recognition is based on the properties inherent to a protein terminus, including the unique chemical epitope presented by the terminal residue and the greater freedom of the terminus to unfold, like the end of a ball of string, to accommodate binding. Insulin recognition was predicted accurately from studies on short peptides and exemplifies an approach to protein recognition by targeting the terminus.